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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/3/2025 has been entered.
Claim Status
Claims 1-4 are pending.
Claims 1-4 are examined.
Priority
This application is a DIV of 18/431,587 02/02/2024
18/431,587 is a CON of 17/340,765 06/07/2021
17/340,765 is a CIP of 17/104,864 11/25/2020
17/104,864 is a CIP of 16/828,681 03/24/2020 ABN
16/828,681 is a CIP of 16/669,151 10/30/2019 ABN
16/669,151 is a CIP of 16/411,944 05/14/2019 ABN
16/411,944 is a DIV of 14/920,392 10/22/2015 PAT 10335452
14/920,392 has PRO 62/151,384 04/22/2015
14/920,392 has PRO 62/068,357 10/24/2014
The SpO2, ACLF, and MELD are first disclosed in APP # 17/340,765; thus, the prior art date of this application is the effective filing date of APP # 17/340,765 on 11/25/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/13/2024, 4/16/2025, 5/15/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Modified Rejection
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Jamil et al. (US 2016/0113994 A1) in view of Sue (Ann Am Thorac Soc Vol 13, No 12, pp 2266–2271, Dec 2016.) in view of (b) Lucassin (Ikaria, Inc. 2012), Wisniewski et al. (US 2016/0122386 A1), and Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734), in view of (c) Liang et al. (Sci Rep. 2017; 7: 42253), and in view of (d) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, previously cited 9/20/2024).
Claim 1 is drawn to a method of treating an adult patient aged 18 years or older with hepatorenal syndrome comprising:
obtaining a baseline oxygenation level (SpO2) from the patient via pulse oximetry;
determining the patient's acute-on-chronic liver failure (ACLF) Grade;
acquiring a baseline model end stage liver disease (MELD) score of the patient;
administering a dose of a composition comprising terlipressin to the patient by intravenous (IV) injection if the patient's SpO2 at baseline is greater than 90%, the ACLF Grade is < 3, and the baseline MELD score is <35;
monitoring the patient's SpO2 during administration of the composition at least 3 times a day; and
discontinuing administration or reducing the dose of the composition if the patient's SpO2 during treatment is less than 90%.
Jamil et al. teach a method of treating patients with hepatorenal syndrome type I with terlipressin (Title and Abstract). Jamil et al. teach the therapeutic composition comprising 1 mg active ingredient and 10 mg mannitol in saline [0019-0020] for bolus or IV injection [0061]. Jamil et al. teach the terlipressin dosage is 1 mg administered intravenously every 6 hours as a slow bolus injection over 2 minutes [0149]. Jamil et al. teach suggest the treated patients can be men and women aged 18 years or older [0161], reading on an adult patient. Jamil et al. teach side effect and complications associated with terlipressin comprising ischemia, pulmonary edema and fluid overload known in the art [0022, col 2] and further suggest administration of terlipressin may require temporary interruption, dose decrease, or permanent discontinuation if adverse events occur [0022, col 1]. Jamil et al. teach patients with HRS-1 are critically ill and terlipressin can have side-effects, to determine if a patient is likely to respond to terlipressin and only treating those patients, can be extremely beneficial and even life-saving as terlipressin is known to be effective in only 33-60% of HRS-1 patients [0022]. Jamil et al. further teach due to Terlipressin’s constrictive effects on smooth muscle, terlipressin should be used with caution in high-risk patients with severe asthma or chronic obstructive pulmonary disease (COPD). Patients with these disorders who receive terlipressin should be closely monitored (reading on continuously monitored) and bronchospasm should be treated symptomatically [0022]. Sue is cited to show common knowledge in the emergency care of using pulse oximetry to measure oxygen saturation of SpO2 and if SpO2 at 89% or lower for a high-risk patient (e.g., asthma) should provide supplemental oxygen to bring SpO2 back to normal range (p2266, col 1, Patient 1, para 2; p2267, para 1).
With respect to the limitation (i) of the baseline SpO2 ≥ 90%, Lucassin teaches terlipressin (synonym of Lucassin) is effective and safe to improve renal function in patients with hepatorenal syndrome type 1 (HRS-1) in clinical trials (p2, last para; p3, Fig 1) in adult patients ranged from 23 to 74 years old (p3, para 1), consistent with Jamil et al. Lucassin suggests terlipressin and other vasopressin analogues reduced blood flow resulting in adverse events of (a) tissue hypoxia without sufficient oxygenation for proper tissue function (p7, para 2) as well as (b) ischaemic events, a condition of reduced blood supply to a tissue or organ (cardiac, gastrointestinal, and skin) leading to a shortage of oxygen and nutrient in tissues/organs, reading on systemic hypoxia (p7, 2nd last para, Adverse effects). Lucassin suggests adverse events of reducing blood flow and shortage of oxygen supply in blood may require temporary interruption, dose decrease or permanent discontinuation of terlipressin to avoid hypoxia including systemic hypoxia and ischaemic events in patients (p6, Ischaemic events), consistent with Jamil et al. [0022]. Wisniewski et al. is further cited as an additional reference to show adverse events of terlipressin comprising tissue hypoxia and ischemia as a common knowledge in the art [0020], consistent with Lucassin’s teaching described above. Because administration of terlipressin was commonly known to cause tissue hypoxia including systemic hypoxia and/or ischemia with low oxygen supply in certain patients demonstrated by Lucassin in view of Wisniewski et al., one of ordinary skill in the art would have found it obvious to beneficially exclude a patient with tissue hypoxia (SpO2 < 90%) and/or ischemia before and during terlipressin treatment. Furthermore, Lucassin explicitly teaches terlipressin should be used with caution due to its constrictive effects on smooth muscle in patients with severe asthma or chronic obstructive pulmonary disease (COPD). Patients with these disorders who require terlipressin should be closely monitored, reading on continuously monitored, and any bronchospasm should be treated symptomatically (Lucassin. p6, Respiratory Effects and p8, respiratory failure), consistent with Jamil et al. [0022]. Sue is cited to show “Treating Hypoxemia with Supplemental Oxygen” (Title). Sue teaches the use of pulse oximetry to measure oxygen saturation (SpO2) for an asthma patient with SpO2 level at 89% (p2266, col 1, patient 1, para 1-2). Sue teaches supplemental oxygen is administered through a face mask with FiO2 at 0.35 for patient 1 to achieve an SpO2 of roughly 94% (p2267, para 1), demonstrating exclusion of a patient with SpO2 of 89% or less by narrowing a patient group with SpO2 > 89% (e.g., SpO2 > 90%) able to beneficially reduce risks of respiratory failure or serious adverse events of terlipressin treatment. Alwadhi et al. is cited to show hypoxia known to be oxygen saturation (SpO2) < 90% and can be easily identified by pulse oximetry known by one of ordinary skill in the art (p729, col 1), consistent with Sue. Because a patient with a baseline SpO2 ≥ 90% without hypoxia or lower than normal oxygen saturation is more beneficial for terlipressin treatment, it would be obvious to exclude a patient with baseline < 90% (hypoxia or hypoxemia or lower than normal oxygen saturation) and ONLY administer terlipressin to a patient’s baseline SpO2 ≥ 90% without hypoxia to enhance the successful rate of treatment.
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With respect to the limitation (ii) of the baseline ACLF grade < 3, Rodriguez et al. teach terlipressin and albumin is the standard of care for classical type-1 hepatorenal syndrome (HRS) not associated with active infections (p955, col 1, Background & Aims). Rodriguez et al. teach patients with associated severe ACLF grade III are unlikely to respond to treatment (p955, col 2, Conclusion) shown as follows (p958, Table 3). Because Rodriguez et al. show patients with severe ACLF grade III unlikely to respond to treatment, it would be obvious to exclude a patient with baseline ACLF grade 3 and ONLY administer terlipressin to a patient’s baseline ACLF grade < 3 to enhance the successful rate of treatment. Rodriguez et al. show terlipressin ONLY administered to patient with baseline SCr <
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5 shown as follows (p957, Table 1), further reading on the limitation (ii). Rodriguez et al. further teach patient’s vital sign assessed at least 3 times daily during terlipressin treatment (p956, col 2, para 2), consistent with the combined teachings of Jamil et al., Sue, Lucassin and Wisniewski et al. Sue and Alwadhi et al. for the use of pulse oximetry to closely/continuously monitoring SpO2 before and during terlipressin treatment to avoid administering terlipressin to a patient with SpO2 < 90% (hypoxia, hypoxemia, low oxygen saturation), reading on claims 9 and 32.
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With respect to the limitation (iii) of the baseline MEDL score < 35, Ling et al. teach MELD presented the best ability in predicting 3-month, 6-month and 1-year mortality, showing a significantly better predictive ability than UKELD and iMELD (Abstract). Ling et al. suggest MELD score can be used to analyze patients with hepatorenal syndrome (p2, Table 1; p6, Table 3). Ling et al. show MELD with great correlation with 3-month death, the lower MELD score the better, as follows (p5, Fig 3), suggesting a patient with lower baseline MELD score is likely to respond to terlipressin. Ling et al. further show even more benefit for survival after liver transplant with lower MEDL shown as follows (p5, Fig 2B). Because Ling et al. show a benefit to exclude patients with MEDL > 35, it would be obvious to beneficially administer terlipressin to ONLY a patient with baseline MELD score < 35 to enhance the successful rate of treatment.
With respect to the limitation (iv), Jamil et al. teach the therapeutic composition comprising 1 mg active ingredient and 10 mg mannitol in saline [0019-0020] for bolus or IV injection [0061]. The benefits of determining a patient likely to respond to terlipressin and only treating those patients as taught by Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. are described above not repeated here. Thus, it would be obvious to exclude patients unlikely to respond to terlipressin treatment and only administer terlipressin to treat patients with SpO2 > 90% without hypoxia, ACLF Grade < 3, and MELD score <35.
With respect to the limitation (v), Lucassin suggests terlipressin and other vasopressin analogues reduced blood flow resulting in adverse events of (a) tissue hypoxia without sufficient oxygenation for proper tissue function (p7, para 2) as well as (b) ischaemic events, a condition of reduced blood supply to a tissue or organ (cardiac, gastrointestinal, and skin) leading to a shortage of oxygen and nutrient in tissues/organs, reading on systemic hypoxia (p7, 2nd last para, Adverse effects). Wisniewski et al. is further cited as an additional reference to show adverse events of terlipressin comprising tissue hypoxia and ischemia as a common knowledge in the art [0020]. Thus, it would be obvious to monitor the baseline SpO2 of patients to avoid initial administration of terlipressin to a patient with hypoxia (SpO2 <90%) and continuously monitor patient’s SpO2 to avoid administration of a patient with hypoxia (SpO2 <90%) or adverse events caused by terlipressin taught by Lucassin. Jamil et al. teach the terlipressin dosage is 1 mg administered intravenously every 6 hours as a slow bolus injection over 2 minutes [0149]. Since terlipressin is administered every 6 hours (4 times a day), it would be obvious to monitor SpO2 of a patients before and/or after administration of terlipressin, reading on at least 4 times a day and consistent with Rodriguez’s teaching of patient’s vital sign assessed at least 3 times daily during terlipressin treatment (p956, col 2, para 2). Furthermore, Jamil et al. teach side effect and complications associated with terlipressin comprising ischemia, pulmonary edema and fluid overload known in the art [0022, col 2]. Lucassin explicitly teaches terlipressin should be used with caution due to its constrictive effects on smooth muscle in patients with severe asthma or chronic obstructive pulmonary disease (COPD). Patients with these disorders who require terlipressin should be closely monitored, reading on continuously monitored, and any bronchospasm should be treated symptomatically (Lucassin. p6, Respiratory Effects and p8, respiratory failure), consistent with Jamil et al. [0022]. Sue is cited to show “Treating Hypoxemia with Supplemental Oxygen” (Title). Sue teaches the use of pulse oximetry to measure oxygen saturation (SpO2) for an asthma patient with SpO2 level at 89% (p2266, col 1, patient 1, para 1-2), providing additional reasons to closely/continuously monitoring SpO2 for high-risk patients though the entire period of terlipressin treatment to avoid administration of terlipressin to patients with hypoxia, hypoxemia, or low oxygen saturation is blood or tissue.
With respect to limitation (vi), Lucassin suggests adverse events of reducing blood flow and shortage of oxygen supply in blood may require temporary interruption, dose decrease or permanent discontinuation of terlipressin to avoid administration of terlipressin to patients with hypoxia including systemic hypoxia and ischaemic events (p6, Ischaemic events), consistent with Jamil et al. [0022].
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Jamil et al. in view of Sue with (ii) Lucassin in view of Wisniewski et al. and Alwadhi et al. because (1) Jamil et al. teach determining if a patient is likely to respond to terlipressin and only treating those patients can be extremely beneficial and even life-saving as terlipressin is known to be effective in 33-60% of HRS-1 patients [0022] and (2) Lucassin suggests terlipressin reduced blood flow resulting in adverse events comprising (i) tissue hypoxia without sufficient oxygenation for proper tissue function (p7, para 2) as well as (ii) ischaemic events, a condition of reduced blood supply to a tissue or organ (cardiac, gastrointestinal, and skin) leading to a shortage of oxygen and nutrient in tissues/organs reading on systemic hypoxia (p7, 2nd last para, Adverse effects), consistent with Wisniewski et al. [0020]. Lucassin further teaches patients with severe asthma or chronic obstructive pulmonary disease (COPD) who require terlipressin should be closely monitored, reading on continuously monitored, and any bronchospasm should be treated symptomatically (Lucassin. p6, Respiratory Effects and p8, respiratory failure), consistent with Jamil et al. Sue teaches common knowledge for the use of pulse oximetry to measure oxygen saturation for an asthma patient with SpO2 level at 89% (p2266, col 1, patient 1, para 1-2) for supplemental oxygen. Alwadhi et al. is cited to show hypoxia known to be oxygen saturation (SpO2) < 90% and can be easily identified by pulse oximetry known by one of ordinary skill in the art (p729, col 1), consistent with Sue. The combination would have reasonable expectation of success because exclusion of a patient with SpO2 < 90% (hypoxia/hypoxemia or lower than normal level of oxygen in blood and/or tissues) and only administration of terlipressin to patients with baseline SpO2 > 90% is expected to beneficially enhance successful rate of treatment, in particular, for the high-risk patients with severe asthma or chronic obstructive pulmonary disease (COPD) taught by Jamil et al. [0022], Lucassin. (p6, Respiratory Effects and p8, respiratory failure), and Sue (p2266, col 1, Patient 1, para 2; p2267,para 1).
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (1) Jamil et al., in view of Sue in view of Lucassin, Wisniewski et al., and Alwadhi et al. with (2) Liang et al., and (3) Rodriguez et al. because (a) Jamail et al. teach patients with HRS-1 are critically ill and terlipressin can have side-effects, to determine if a patient is likely to respond to terlipressin and only treating those patients can be extremely beneficial and even life-saving as terlipressin is known to be only effective in 33-60% of HRS-1 patients [0022], (b) Ling et al. show MELD with great correlation with 3-month death, the lower MELD score the better, (p5, Fig 3), suggesting a patient with lower baseline MELD score is likely to respond to terlipressin. Ling et al. further show even more benefit for survival after liver transplant with lower MEDL (p5, Fig 2B), and (c) Rodriguez et al. teach patients with associated severe ACLF grade III are unlikely to respond to treatment (p955, col 2, Conclusion; p958, Table 3). The combination would have reasonable expectation of success because all references teach or suggest a subset patient group having better response to terlipressin treatment.
Thus, Jamil et al. (US 2016/0113994 A1) in view of Sue (Ann Am Thorac Soc Vol 13, No 12, pp 2266–2271, Dec 2016.) in view of (b) Lucassin (Ikaria, Inc. 2012, previously cited 8/24/2023), Wisniewski et al. (US 2016/0122386 A1), and Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734), in view of (c) Liang et al. (Sci Rep. 2017; 7: 42253), and in view of (d) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, previously cited 9/20/2024) is obvious to the instant claims 1-4.
Applicant’s Arguments
The Examiner's arguments are fully rebutted by the expert declaration of record from a medical doctor for the rejection based on Krag, Majumdar, Rodriguez, and/or Alessandria (Remarks, p5, para 2 to p13, para 1-2).
Evidence of Non-Obviousness Substantially Outweighs Obviousness: Unexpected Results and Long-Felt Need Have Been Established by 1.132 Declaration (Remarks, p13, last para to Declaration #1-#13).
Response to Arguments
Applicant's arguments filed 3/3/2025 have been fully considered but they are not persuasive because the arguments (i) and (ii) do not apply to the modified rejection based on Jamil et al. (US 2016/0113994 A1) in view of Sue (Ann Am Thorac Soc Vol 13, No 12, pp 2266–2271, Dec 2016.) in view of (b) Lucassin (Ikaria, Inc. 2012, previously cited 8/24/2023), Wisniewski et al. (US 2016/0122386 A1), and Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734), in view of (c) Liang et al. (Sci Rep. 2017; 7: 42253), and in view of (d) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, previously cited 9/20/2024).
Furthermore, applicant’s declaration did not provide any persuasive data to support the opinion of unexpected result and certain arguments of applicant’s declaration are not in compliance with MPEP. For example, Declaration #10 is an unreasonable argument of improperly combining four references. In addition, there is no “unexpected result” as argued by applicant for the reasons as taught by the cited references summarized as follows:
Jamil et al. teach patients with HRS-1 are critically ill and terlipressin can have side-effects, to determine if a patient is likely to respond to terlipressin and only treating those patients, can be extremely beneficial and even life-saving as terlipressin is known to be effective in only 33-60% of HRS-1 patients [0022]. Administration of terlipressin was commonly known to cause tissue hypoxia including systemic hypoxia and/or ischemia with low oxygen supply in certain patients demonstrated by Lucassin in view of Wisniewski et al. Sue is cited to show “Treating Hypoxemia with Supplemental Oxygen” (Title). Sue teaches the use of pulse oximetry to measure oxygen saturation (SpO2) for an asthma patient with SpO2 level at 89% (p2266, col 1, patient 1, para 1-2) even without administering terlipressin. Thus, it is an expected benefit to exclude patients with SpO2<90% (hypoxia, hypoxemia, or lower than normal oxygen saturation in blood or tissues) from terlipressin treatment to increase successful rate of treatment.
Alwadhi et al. is cited to show hypoxia known to be oxygen saturation (SpO2) < 90% and can be easily identified by pulse oximetry known by one of ordinary skill in the art (p729, col 1), consistent with Sue.
Rodriguez et al. teach patients with associated severe ACLF grade III are unlikely to respond to treatment (p955, col 2, Conclusion) shown as follows (p958, Table 3). Thus, it is an expected benefit to exclude patients with ACLF grade III from terlipressin treatment to increase successful rate of treatment.
Ling et al. show a benefit to exclude patients with MEDL > 35, it would be obvious to beneficially administer terlipressin to ONLY a patient with baseline MELD score < 35 to enhance the successful rate of treatment. Thus, it is an expected benefit to exclude patients with MELD score > 35 from terlipressin treatment to increase successful rate of treatment. See MPEP 2144(II) The expectation of some advantage is the strongest rationale for combining references.
Additional references listed in the following are further cited to show the common knowledge level of ordinary skill in the art with respect to administration of 1 mg terlipressin acetate to treat patients with hepatorenal syndrome.
Boyer et al. (J Hepatol. 2010 Dec 15;55(2):315–321) teach the treatment effect of terlipressin vs. placebo appeared to be greatest in the 3-5 mg/di baseline SCr group.
NCT02770716-2019 teaches 1 mg terlipressin acetate and 10 mg mannitol reconstituted in 5 ml 0.9% sodium chloride solution for intravenous bolus injection over 2 minutes every 6 hours (p7, Arms and Interventions). Terlivaz 2023 is cited as evidence to show inherent properties of the administered 1 mg terlipressin acetate with respect to molecular formula and pharmacodynamics and pharmacokinetics.
Pedersen et al. (Cochrane Database Syst Rev. 2014 Mar 17;2014(3):CD002013) shows hypoxia clinically defined as arterial oxygen < 7.8 kPa, SaO2 < 90%, or SpO2 < 90% (consistent with Lange’s teaching of SpO2 strongly correlated to arterial blood oxygen saturation) as a common knowledge of an ordinary skill in the medical field (p19, Moller 1993b, Outcomes) even though local tissue hypoxia, local ischemia, and systemic hypoxia are not identical.
Kwasnicki et al. (Journal of Plastic, Reconstructive & Aesthetic Surgery (2018) 71, 1823) teach the use of pulse oximetry to diagnose limb ischaemia as a common knowledge of an ordinary skill in the medical field (Abstract; Fig 1-2) even though local tissue hypoxia, local ischemia, and systemic hypoxia are not identical.
Rao et al. (Annals of Emergency Medicine, Volume 58, Issue 4, S208 Abstract 93) teach the use of pulse oximetry as a quick screening tool for limb ischemia in the emergency department based on SpO2 level as a common knowledge of an ordinary skill in the medical field, even though local tissue hypoxia, local ischemia, and systemic hypoxia are not identical.
Wong et al. (N Engl J Med 2021;384:818-828) teach terlipressin inherently increasing risk of respiratory failure, consistent with Lucassin (p8, Table 2).
New Ground of Rejection
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 1-4 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of copending Application No. 19/213,363 (the ‘363 application) in view of Jamil et al. (US 2016/0113994 A1) in view of Sue (Ann Am Thorac Soc Vol 13, No 12, pp 2266–2271, Dec 2016.) in view of (b) Lucassin (Ikaria, Inc. 2012, previously cited 8/24/2023), Wisniewski et al. (US 2016/0122386 A1), and Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734), in view of (c) Liang et al. (Sci Rep. 2017; 7: 42253), and in view of (d) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, previously cited 9/20/2024).
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Claim 1 of the ‘363 application disclosed a method of treating an adult patient with hepatorenal syndrome to improve kidney function as follows.
Claim 5 of the ‘363 application disclosed the SpO2 level is monitored continuously during administration.
Claims 1 and 5 of the ‘363 application do not disclose the treated patients with baseline MEDL score < 35.
The relevancy of Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. as applied to claims 1-4 described above not repeated here.
Because Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. teach only beneficially treating patients likely to respond to terlipressin treatment, one of ordinary skill in the art would have found it obvious to combine claims 1 and 5 of the ‘363 application with Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. to treat patients likely to respond to terlipressin treatment.
Thus, claims 1 and 5 of the ‘363 application in view of Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. are obvious to the instant claims 1-4.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/244,769 (the ‘769 application) in view of Jamil et al. (US 2016/0113994 A1) in view of Sue (Ann Am Thorac Soc Vol 13, No 12, pp 2266–2271, Dec 2016.) in view of (b) Lucassin (Ikaria, Inc. 2012, previously cited 8/24/2023), Wisniewski et al. (US 2016/0122386 A1), and Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734), in view of (c) Liang et al. (Sci Rep. 2017; 7: 42253), and in view of (d) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, previously cited 9/20/2024).
Claim 1 of the ‘769 application disclosed a formulation of terlipressin acetate of C52H14N16O15S2 • (C2H4O2)n, wherein n is between 1.0 to 3.5.
Claim 1 of the ‘769 application did not teach administration of terlipressin acetate to treat hepatorenal syndrome.
The relevancy of Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. as applied to claims 1-4 described above not repeated here. Furthermore, Lucassin teaches the terlipressin acetate comprising terlipressin free base and approximately two equivalent acetic acid (p1, description), reading on n about 2.
Because Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. teach only beneficially treating patients likely to respond to terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially combine claim 1 of the ‘769 application with Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. to treat patients likely to respond to terlipressin treatment.
Thus, claim 1 of the ‘769 application in view of Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. are obvious to the instant claims 1-4.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/244,777 (the ‘777 application) in view of Jamil et al. (US 2016/0113994 A1) in view of Sue (Ann Am Thorac Soc Vol 13, No 12, pp 2266–2271, Dec 2016.) in view of (b) Lucassin (Ikaria, Inc. 2012, previously cited 8/24/2023), Wisniewski et al. (US 2016/0122386 A1), and Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734), in view of (c) Liang et al. (Sci Rep. 2017; 7: 42253), and in view of (d) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, previously cited 9/20/2024).
Claim 1 of the ‘777 application disclosed a formulation of terlipressin acetate of C52H14N16O15S2 • (C2H4O2)n, wherein n is between 1.0 to 3.5 and 0.01%-1% SEQ ID Nos: 3-12.
Claim 1 of the ‘777 application did not teach administration of terlipressin acetate to treat hepatorenal syndrome.
The relevancy of Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. as applied to claims 1-4 described above not repeated here. Furthermore, Lucassin teaches the terlipressin acetate comprising terlipressin free base and approximately two equivalent acetic acid (p1, description), reading on n about 2.
Because Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. teach only beneficially treating patients likely to respond to terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially combine claim 1 of the ‘777 application with Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. to treat patients likely to respond to terlipressin treatment.
Thus, claim 1 of the ‘777 application in view of Jamil et al. in view of Sue in view of (b) Lucassin, Wisniewski et al., and Alwadhi et al., in view of (c) Liang et al., and in view of (d) Rodriguez et al. are obvious to the instant claims 1-4.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/J.L/Examiner, Art Unit 1658
12-July-2025
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654