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 .
Claim Status
Claims 53-82 are pending.
Claims 1-52 are cancelled.
Claims 53-82 have been examined.
Priority
This application 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
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The prior art date of the instant claims is 6/7/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 7/21/2025 and 1/15/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Withdrawn Objection and Rejection
All objection and rejections are withdrawn as a result of claim amendments.
New Ground of 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 53, 55 and 58-63 are rejected under 35 U.S.C. 103 as being unpatentable over Jamail et al. (US 2016/0113994 A1) in view of Lucassin (Ikaria, Inc. 2012, previously cited 6/1/2023), Wisniewski et al. (US 2016/0122386 A1, previously cited 6/1/2023), Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734, previously cited 7/15/2025), Ling et al. (Sci Rep. 2017; 7: 42253, cited in IDS 7/21/2025), Alessandria et al. (Hepatology 2005;41:1282-1289.), Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, cited in IDS 3/23/2022), Bota et al. (J Emerg Med. 1995 May-Jun;13(3):305-11) and NCT02770716 (Version 13, 2018-08-09).
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Claim 53 is drawn to a method of administering terlipressin to a selected patient population with hepatorenal syndrome and the method is capable of increasing life expectancy of pre-selected patients with clinical indicators of SpO2 ≥ 90% , MELD score < 35, and ACLF grade < 3 compared to patients not satisfying the same clinical indicators comprising the steps (a) to (e) shown above.
Jamail et al. teach method of treating patient with hepatorenal syndrome type I, HRS-1, (Title). Jamail et al. teach to avoid the unnecessary administration of drug to patients who are critically ill because of terlipressin is very effective in patients exhibiting certain criteria but is not effective in patients that do not meet this criteria. Possible warnings and precautions associated with terlipressin include ischemia. Ischemic events (cardiac, gastrointestinal, and skin) can occur following administration of terlipressin and may require temporary interruption, dose decrease, or permanent discontinuation. Since 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 33-60% of HRS-1 patients. Jamail et al. teach adverse reaction in more than 10% patients included vomiting, abdominal pain, nausea, diarrhea, intestinal ischemia, dyspnea, sneezing, pulmonary edema and fluid overload known in the art. All conditions that could be severely detrimental to already fragile patients with HRS-1 [0022]. Thus, one of ordinary skill in the art would have found it obvious to (a) identify a patient likely to respond to terlipressin and only treat those selected patients expected to be beneficial and even life-saving with terlipressin as well as (b) reduce the incidence of adverse events in critically ill HRS-1 patients associated with administered terlipressin by excluding patients unlikely to respond to terlipressin treatment, reading on a method of administering terlipressin to a selected patient population with hepatorenal syndrome and the method is capable of increasing life expectancy of pre-selected patients.
Jamail et al. do not specify a selected patient group with a baseline of SpO2 ≥ 90%, a baseline of MELD score< 35, a baseline of ACLF grade< 3, and no cardiac or mesenteric ischemia.
With respect to the limitation (a), Lucassin teaches administration of terlipressin to treat patients with hepatorenal syndrome type 1 (p2, Clinical trials) with mean MELD score 33.4 less than 35 as claimed (p3, para 1). Lucassin teaches administration of terlipressin at an initial dose of 0.85 mg (one vial of Lucassin) every 6 hours (p3, para 1). Lucassin further teaches (i) terlipressin should not be used in patients with unstable angina or recent acute myocardial infarction and (ii) ischaemic events (cardiac, gastrointestinal, and skin) have occurred following administration of terlipressin resulting in reducing blood supply to tissue causing tissue damage (defined as ischemia) and may require temporary interruption, dose decrease or permanent discontinuation of terlipressin (p6, Ischaemic Events). Lucassin further teaches terlipressin and other vasopressin analogues reduced blood flow to tissues resulting in tissue damage such as ischaemia in various tissues (p9, Table 3) due to hypoxia causing insufficient oxygen in body tissue and blood (p7, para 2) and further evidenced by Wisniewski et al. showing adverse events of hypoxia and ischemia as an adverse event of administering terlipressin known in the art [0020], consistent with Lucassin.
Alwadhi et al. teach Oxygen saturation (SpO2) was measured by a pulse oximeter and a clinical predictor of hypoxia is SpO2 <90% (p729, col 1, Methods). Thus, one of ordinary skill in the art would have found it obvious to measure baseline of SpO2 and administer terlipressin only to a patient with baseline of SpO2 ≥ 90% to avoid terlipressin administration to a patient with hypoxia and/or ischemia as measured by pulse oximeter, reading on terlipressin treated patients with baseline SpO2 ≥ 90% without cardiac or mesenteric ischemia.
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).
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Because Ling et al. suggest a benefit to exclude patients with MEDL ≥ 35 to reduce rate of patient death during terlipressin treatment, it would be obvious to beneficially administer terlipressin to ONLY a patient with baseline MELD score < 35 to enhance the successful rate of treatment. Similarly, Alessandria et al. teach “MELD Score and Clinical Type Predict Prognosis in Hepatorenal Syndrome: Relevance to Liver Transplantation” (Title). Alessandria et al. show 3-month survival prediction of HRS is a function of MELD score (p1285, Fig 4). The lower MELD score has a higher 3-month survival probability consistent with Ling et al. One of
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ordinary skill in the art would select a patient group with baseline MELD score at about 30 (less than 35) to cover both type I and type II HRS patients as taught by Alessandria et al. with predictable increase of survival rate consistent with Ling’s Figures 2B and 3.
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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 (ACLF Grade = 3) are unlikely to respond to terlipressin treatment (p955, col 2, Conclusion; p960, col 2, para 4) shown above (p958, col 2, Table 3). Rodriguez et al. teach patients were carefully evaluated every day during treatment for early signs of side effects to terlipressin (p956, col 1, last para to col 2, para 1). Thus, one of ordinary skill in the art would have found it obvious to administer terlipressin only to a patient with baseline of ACLF grade < 3.
With respect to the limitation (b), Alwadhi et al. teach Oxygen saturation (SpO2) was measured by a pulse oximeter with clinical predictors of hypoxia (SpO2 <90%). Bota et al. teach the continuous measurement of arterial oxygen saturation using pulse oximetry ( SpO2) has become popular for critically ill hospitalized patients (Abstract). Bota et al. teach this technology has the added benefit of providing a continuous and immediately available record of oxygen saturation, so that changes in oxygenation (deterioration and improvement) may be observed and acted upon (p306, col 1, para 3). Because (a) hypoxia (SpO2 <90%) and ischaemia are known adverse events of terlipressin administered every 6 hours as taught by Lucassin (p3, para 1) and (b) Rodriguez et al. teach patients were carefully evaluated every day during treatment for early signs of side effects to terlipressin (p956, col 1, last para to col 2, para 1), one of ordinary skill in the art would have found it obvious to beneficially use continuous pulse oximetry to constantly monitor patient’s SpO2 level during terlipressin treatment to prevent administration of terlipressin to a patients with hypoxia and/or ischemia as a result of adverse events of administered terlipressin taught by the cited arts above.
With respect to the limitation (c), Jamil et al teach known common adverse reaction in more than 10% patients included intestinal ischemia, pulmonary edema and fluid overload [0022], consistent with Lucassin’s Table 4 (p10) shown as follows. Thus, one of ordinary skill in the art would have found it obvious to constantly monitoring the common adverse events of
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blood oxygen saturation (SpO2) and fluid overload during terlipressin treatment.
With respect to the limitation (d), Jamil et al teach measuring the patient's serum creatinine (SCr) level during administration of the pharmaceutical composition until at least one SCr value of <1.5 mg/dL is obtained [0053]. Rodriguez et al. show measurement of serum creatinine (SCr) every day during the treatment period of terlipressin (Fig. 1A).
With respect to the limitation (e), it would be obvious to discontinue terlipressin administration to a patient with ischaemic or hypoxia (SpO2 <90%) as taught by Lucassin (p6, Ischaemic Events). NCT02770716 is cited to show HRS versal can be determined by 2 consecutive SCr values ≤ 1 .5 mg/dL at least two hours apart up to 14 days (p7, Primary Outcome Measures).
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Jamail et al. and (ii) Lucassin in view of Wisniewski et al. and Alwadhi et al. because (a) Jamail et al. teach administration of terlipressin to a pre-selected patient group with better response and less probability of developing adverse events in response terlipressin treatment of hepatorenal syndrome, (b) Lucassin teaches administration of terlipressin to treat patients with hepatorenal syndrome, but ischaemic events (cardiac, gastrointestinal, and skin) have occurred following administration of terlipressin resulting in reducing blood supply to tissue causing tissue damage (defined as ischemia) and terlipressin reduces blood flow to tissues resulting in tissue damage such as ischaemia in various tissues (p9, Table 3) due to hypoxia causing insufficient oxygen in body tissue and blood (p7, para 2) and (c) Wisniewski et al. is cited as evidence to show hypoxia and ischemia as an adverse event of administering terlipressin known in the art [0020], consistent with Lucassin, and (d) Alwadhi et al. teach Oxygen saturation (SpO2) was measured by a pulse oximeter and a clinical predictor of hypoxia is SpO2 <90% (p729, col 1, Methods). The combination would have reasonable expectation of success because all references teach adverse events of terlipressin and the adverse event of hypoxia can be measured by pulse oximetry.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Jamail et al. in view of Lucassin, Wisniewski et al. and Alwadhi et al. with (ii) Ling et al. in view of Alessandria et al., Rodriguez et al., and Bota et al. because (a) Jamail et al. teach excluding patients unlikely to respond to terlipressin treatment and administering terlipressin to a selected patient population with hepatorenal syndrome to increase life expectancy of pre-selected patients after terlipressin treatment (b) Ling et al. in view of Alessandria et al. teach MELD score can be used to analyze patients with hepatorenal syndrome (Ling et al. p2, Table 1; p6, Table 3) and 3-month survival prediction of HRS is a function of MELD score (Alessandria et al. p1285, Fig 4), consistent with Ling’s teaching that the lower MELD score has a higher 3-month survival probability, (c) Rodriguez et al. teach patients with associated severe ACLF (ACLF Grade = 3) are unlikely to respond to terlipressin treatment (p955, col 2, Conclusion; p958, col 2, Table 3; p960, col 2, para 4) and further teach patients were carefully evaluated every day during treatment for early signs of side effects to terlipressin (p956, col 1, last para to col 2, para 1) and (d) Bota et al. teach the continuous measurement of arterial oxygen saturation using pulse oximetry (SpO2) has become popular for critically ill hospitalized patients (Abstract). Bota et al. teach this technology has the added benefit of providing a continuous and immediately available record of oxygen saturation, so that changes in oxygenation (deterioration and improvement) may be observed and acted upon (p306, col 1, para 3). The combination would have reasonable expectation of success because (a) excluding patients unlikely to response to terlipressin treatment (higher MELD score than 36-40 with lower survival rate taught by Ling et al. in view of Alessandria et al. and ACLF grade =3 taught by Rodriguez et al.) is expected to increase success of terlipressin treatment resulting in increase of life expectancy of patients with hepatorenal syndrome and (b) Bota’s continuous pulse oximetry adds benefit of providing a continuous and immediately available record of oxygen saturation to avoid administration of terlipressin to a patient with SpO2 < 90% to reduce adverse events of ischemia/hypoxia.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., and Bota et al. with (ii) NCT02770716 because (a) Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., and Bota et al. teach continuous administration of terlipressin until reversal of HRS-1 with SCr level to ≤ 1.5 mg/dl [Jamil 0035] and (b) NCT02770716 is cited to show HRS versal can be determined by 2 consecutive SCr ≤ 1.5 mg/dL at least two hours apart (p7, Primary Outcome Measures). The combination would have reasonable expectation of success because both Jamail et al. and NCT02770716 teach reversal of HRS-1 with SCr level to ≤ 1.5 mg/dl.
With respect to claim 55, Jamil et al. teach terlipressin can be administered alone or together with albumin [0085] consistent with Lucassin (p8, Table 2; p10, Table 4).
With respect to claims 58-59, Lucassin teaches management of suspected adverse drug reactions may require temporary interruption (discontinue administration) and/or dose reduction (p11, Dosage and Administration). Lucassin teaches fluid overload is one of comment adverse events of terlipressin administration (p8, Table 2; p9, Table 3; p10, Table 4) consistent with Jamil [0022]. Rodriguez et al. teach patients were carefully evaluated every day during treatment for early signs of side effects to terlipressin (p956, col 1, last para to col 2, para 1).
With respect to claims 60-63, Lucassin teaches the recommended starting dose is one vial of LUCASSIN (0.85 mg terlipressin) every 6 hours by slow intravenous bolus injection. If serum creatinine (SCr) of a patient has not decreased by at least 30% from the baseline value after 3 days (reading on day 4), the dose can be increased to two vials of LUCASSIN (1.7 mg terlipressin) every 6 hours (p11, Dosage and Administration, para 1). It would be obvious to continue administration of 0.85 mg terlipressin to a patient’s baseline of SCr more than 30% until reversal of HRS-1 with 2 consecutive SCr ≤ 1.5 mg/dL at least two hours apart.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection described above. In particular, FDA’s regulations are irrelevant to patent examination. Furthermore, Jamil et al. teach the only effective and permanent treatment for end-stage cirrhosis and HRS is liver transplantation [0037]. Thus, the long-felt need is providing more liver organs to shorten the waiting period of liver transplantation for patients with end-stage cirrhosis and HRS as taught by Jamil et al. Merely increasing the probability of patient’s survival before liver transplantation is NOT equal to liver transplantation. The combined references teach administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment with reduced risk of developing adverse events to increase the probability of patient’s survival before liver transplantation as claimed.
Claims 53-55, 58-76, and 78-82 are rejected under 35 U.S.C. 103 as being unpatentable over Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al. and NCT02770716 as applied to claims 53, 55, 58-63, and further in view of Boyer et al. (Journal of Hepatology. 2011; 55: 315-321, previously cited 7/15/2025).
Claim 54 is directed to the patient has a baseline serum creatine (SCr) level of ≤ 5 mg/dL.
Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al. and NCT02770716 teach administration of terlipressin to a pre-selected patient with hepatorenal syndrome likely to respond to terlipressin treatment.
Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al. and NCT02770716 do not specify a patient with baseline serum creatinine < 5.0 mg/dl likely to respond to terlipressin treatment.
Boyer et al. teach administration of terlipressin plus albumin is effective in reversing type 1 HRS as compared to albumin alone. However, only about 1 /3 of patients respond to treatment, therefore, predictors of response and survival would help identify the patients most likely to benefit from treatment (p315, col 1, Background & Aims), consistent with Jamail et al. [0022]. Boyer et al. teach the most consistent predictor of response to terlipressin and of survival is the baseline serum creatinine (SCr). Patients most likely to benefit from terlipressin have earlier onset renal failure with serum creatinine < 5.0 mg/dl (p315, col 1, Conclusions). Thus, one of ordinary skill in the art would have found it obvious to administer terlipressin only to a selected patient with baseline of SCr < 5.0 mg/dl, reading on claim 54.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al. and NCT02770716 and (ii) Boyer’s teaching of baseline serum creatinine < 5.0 mg/dl because (a) Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al. and NCT02770716 teach administration of terlipressin to a pre-selected patient with hepatorenal syndrome likely to respond to terlipressin treatment and (b) Boyer et al. teach the most consistent predictor of response to terlipressin and of survival is the baseline serum creatinine (SCr). Patients most likely to benefit from terlipressin have earlier onset renal failure with serum creatinine < 5.0 mg/dl (p315, col 1, Conclusions). The combination would have reasonable expectation of success because all Jamil et al., Ling et al., Alessandria et al., Rodriguez et al. and Boyer et al. teach selected patient groups likely to respond to terlipressin treatment.
With respect to claim 64, Jamil et al. teach patients with HRS Type-1 may die from renal failure while waiting for a liver transplant known in the art [0003] and terlipressin is known to be effective in 33-60% HRS-1 patients [0022]. This, it is expected that a pre-selected patient likely to respond to terlipressin treatment as taught by the combined references of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. would increasing life expectancy reducing pre-liver-transplant mortality during the waiting period of liver transplantation. The limitation of steps (a) and (b) in claim 64 as taught by Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. have been described above not repeated here. Step (c) in claim 64 are patients unlikely to respond to terlipressin treatment taught by the same references; thus, patients of step (c) are excluding from terlipressin treatment. The wherein clause is directed to a patients excluding from terlipressin treatment; thus it does not play a patent weight to reduce pre-liver-transplant mortality.
With respect to claims 65-66, Lucassin shows common adverse events of terlipressin treatment including respiratory failure, ischemia, and fluid overload (p8, Table 2)
With respect to claim 67, Lucassin teaches the recommended starting dose is one vial of LUCASSIN (0.85 mg terlipressin) every 6 hours by slow intravenous bolus injection (p11, Dosage and Administration, para 1).
With respect to claims 68-70, See rationale to measure baseline SpO2 taught by Lucassin, Wisniewski et al., Alwadhi et al., and Bota et al. to include patients with baseline SpO2 ≥ likely to respond to terlipressin treatment and exclude patients with baseline SpO2 < 90% with risk of developing adverse events of hypoxia and/or ischemia described above not repeated here.
With respect to claim 71, Lucassin teaches each vial of Lucassin contains 0.85 mg sterile, lyophilized powder together with mannitol and acetate salt for reconstitution (p1, Description).
With respect to claim 72, NCT02770716 teach 1 mg lyophilized terlipressin acetate formulated with 10 mg mannitol compared to 11 mg mannitol as the placebo in the clinical trial (p7, Arms and Interventions).
With respect to claims 73-74, Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach administration of terlipressin to treat a pre-selected patient group likely to respond to terlipressin treatment with baselines of MEDL <35, ACLF grade <3, SCr level < 5 mg/dL, and SpO2 ≥ 90% described above not repeated here. Because the pre-selected patients are more likely to respond to terlipressin treatment with success treatment to increase life expectancy for a patient with hepatorenal syndrome, it is expected for the pre-selected patients has a reduced risk of dying due to an adverse event compared to patients treated by terlipressin without pre-selection. For example, excluding terlipressin treatment to a patient with SpO2 < 90% is expected to reduce adverse event of death from hypoxia/ischemia associated with terlipressin treatment.
With respect to claim 75, Jamil et al. teach terlipressin can be administered alone or together with albumin [0085] consistent with Lucassin (p8, Table 2; p10, Table 4).
With respect to claims 76 and 78-79, Lucassin teaches management of suspected adverse drug reactions may require temporary interruption (discontinue administration) and/or dose reduction (p11, Dosage and Administration). Lucassin teaches fluid overload is one of comment adverse events of terlipressin administration (p8, Table 2; p9, Table 3; p10, Table 4) consistent with Jamil [0022]. Rodriguez et al. teach patients were carefully evaluated every day during treatment for early signs of side effects to terlipressin (p956, col 1, last para to col 2, para 1).
With respect to claim 80, See rationale to measure baseline SpO2 taught by Lucassin, Wisniewski et al., Alwadhi et al., and Bota et al. to include patients with baseline SpO2 ≥ likely to respond to terlipressin treatment and exclude patients with baseline SpO2 < 90% with risk of developing adverse events of hypoxia and/or ischemia described above not repeated here. In particular, Rodriguez et al. teach patients were carefully evaluated every day during treatment for early signs of side effects to terlipressin (p956, col 1, last para to col 2, para 1).
With respect to claims 81-82, Alwadhi et al. teach Oxygen saturation (SpO2) was measured by a pulse oximeter with clinical predictors of hypoxia (SpO2 <90%). Thus, it would be obvious to discontinue administration to a patient having adverse event of hypoxia with baseline of SpO2 <90%. Bota et al. teach the continuous measurement of arterial oxygen saturation using pulse oximetry has become popular for critically ill hospitalized patients (Abstract). Bota et al. teach this technology has the added benefit of providing a continuous and immediately available record of oxygen saturation, so that changes in oxygenation (deterioration and improvement) may be observed and acted upon (p306, col 1, para 3).
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection. See response to arguments above.
Claims 53-56 and 58-82 are rejected under 35 U.S.C. 103 as being unpatentable over Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716 and Boyer et al. as applied to claims 53-55, 58-76, 78-82 and further in view of Pulimood et al. (Crit Care 2000, 4:151–155).
Claims 56 and 77 are drawn to discontinuation of albumin administration to a patient with adverse event of fluid overload.
Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716 and Boyer et al. teach administration of terlipressin and albumin to treat pre-selected patients with hepatorenal syndrome.
Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716 and Boyer et al. did not specify when to discontinue administration of albumin.
Pulimood et al. teach administration of albumin can result in fluid overload (p153, col 1, para 2) and further suggest death with albumin might be fluid overload (p154, col 2, para 1). Because albumin can cause fluid overload leading to death, one of ordinary skill in the art would have found it obvious to discontinue administration of albumin after the patient experiences fluid overload, reading on claims 56 and 77.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716 and Boyer et al. teach administration of terlipressin and albumin to treat pre-selected patients with hepatorenal syndrome and (b) Pulimood et al. teach administration of albumin can result in fluid overload (p153, col 1, para 2) and further suggest death with albumin might be fluid overload (p154, col 2, para 1). The combination would have reasonable expectation of success because discontinuation of albumin administration is able to eliminate albumin-mediated fluid overload and death in patients.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection. See response to arguments above.
Claims 53-55, 57-76, and 78-82 are rejected under 35 U.S.C. 103 as being unpatentable over Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716 and Boyer et al. as applied to claims 53-55, 58-76, and 78-82, and further in view of Photia et al. (Journal of Blood Medicine 2020:11 503-513).
Claim 57 is drawn to administration of diuretics to the patient experiencing fluid overload.
Jamail et al. in view of Lucassin teach pulmonary oedema and fluid overload resulting from adverse event of terlipressin treatment.
Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716 and Boyer et al. do not specify administration of diuretics to treat fluid overload.
Photia et al. teach furosemide is a loop diuretic and has been used to treat volume overload and high blood pressure. Photia et al. teach practical use of furosemide include acute pulmonary edema, chronic congestive heart failure, hypertension and hyperkalemia (p504, col 2, para 2). Because Photia et al. teach beneficial use of a loop diuretic furosemide to treat volume overload and pulmonary edema, one of ordinary skill in the art would have found it obvious to administer Photia’s loop diuretic of furosemide to treat fluid overload and/or pulmonary edema resulting from the adverse event of terlipressin treatment, reading on claim 57.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716 and Boyer et al. with Photia et al. because (a) Jamail et al. in view of Lucassin teach pulmonary oedema and fluid overload resulting from adverse event of terlipressin treatment and (b) Photia et al. teach beneficial use of a loop diuretic furosemide to treat volume overload and pulmonary edema (p504, col 2, para 2). The combination would have reasonable expectation of success because Photia et al. teach volume overload and pulmonary edema can be treated by a loop diuretic furosemide.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection. See response to arguments above.
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 53-55, 58-76, and 78-82 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-6 of U.S. Patent No. 10,335,452 B2 (the ‘452 patent) in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. (cited in the 2nd 103 rejection above).
Claim 1 of the ‘452 patent disclosed administration to treat a patient with type I hepatorenal syndrome.
Claims 5-6 of the ‘452 patent disclosed the dosage of administered terlipressin in the range of 0.5 mg to 2.0 mg every 4 to 6 hours.
Claims 1 and 5-6 of the ‘452 patent do not disclose administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment with baseline SpO2 ≥ 90%, MEDL score <35, ACLF grade < 3 and monitoring fluid overload during the treatment.
The relevancy of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. as applied to claims 53-55, 58-76, and 78-82 not repeated here.
Because Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach beneficial administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment to increase life expectancy of treated patients, one of ordinary skill in the art would have found it obvious to beneficially administer terlipressin taught by claims 1 and 5-6 of the ‘452 patent to treat the pre-selected patients taught by the cited references.
Thus, claims 1 and 5-6 of the ‘452 patent in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. are obvious to the instant claims 53-55, 58-76, and 78-82.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because applicant’s request of this rejection held in abeyance until rejections are overcomes does not overcome this rejection.
Claims 53-55, 58-76, and 78-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44 and 48 of copending Application No. 17/104,864 (the ‘864 application, 2/17/2016) in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. (cited in the 2nd 103 rejection above).
Claim 44 of the ‘864 application disclosed administering terlipressin to a patients with baseline SCr < 5 mg/dl and ACLF grade < 3 as well as monitoring fluid overload and oxygen saturation during terlipressin treatment.
Claim 48 is drawn to the patient is also administered albumin.
Claims 44 and 48 of the ‘864 application do not disclose baseline of MEDL score.
The relevancy of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. as applied to claims 53-55, 58-76, and 78-82 not repeated here.
Because Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach beneficial administration of terlipressin to a pre-selected patient group with MEDL score < 35 likely to respond to terlipressin treatment to increase life expectancy of treated patients, one of ordinary skill in the art would have found it obvious to beneficially administer terlipressin taught by claims 44 and 48 of the ‘864 application to treat the pre-selected patients taught by the cited references.
Thus, claims 44 and 48 of the ‘864 application in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. are obvious to the instant claims 53-55, 58-76, and 78-82.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because applicant’s request of this rejection held in abeyance until rejections are overcomes does not overcome this rejection.
Claims 53-55, 58-76, and 78-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/587,442 (the ‘442 application, 12/30/2025) in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. (cited in the 2nd 103 rejection above).
Claim 1 of the ‘442 application disclosed a method of administering terlipressin to a patient with type-1 hepatorenal syndrome via IV route every 6 hours.
Claim 1 of the ‘442 application does not disclose administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment with baseline SpO2 ≥ 90%, MEDL score <35, ACLF grade < 3 and monitoring fluid overload during the treatment.
The relevancy of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. as applied to claims 53-55, 58-76, and 78-82 not repeated here.
Because Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach beneficial administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment to increase life expectancy of treated patients, one of ordinary skill in the art would have found it obvious to beneficially administer terlipressin taught by claim 1 of the ‘442 application to treat the pre-selected patients taught by the cited references.
Thus, claim 1 of the ‘442 application in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. are obvious to the instant claims 53-55, 58-76, and 78-82.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because applicant’s request of this rejection held in abeyance until rejections are overcomes does not overcome this rejection.
Claims 53-55, 58-76, and 78-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44 and 48 of copending Application No. 17/976,502 (the ‘502 application, 9/24/2025) in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. (cited in the 2nd 103 rejection above).
Claim 1 of the ‘502 application disclosed a method of administering terlipressin to treat an adult patient with hepatorenal syndrome.
Claim 1 of the ‘502 application does not disclose administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment with baseline SpO2 ≥ 90%, MEDL score <35, ACLF grade < 3 and monitoring fluid overload during the treatment.
The relevancy of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. as applied to claims 53-55, 58-76, and 78-82 not repeated here.
Because Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach beneficial administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment to increase life expectancy of treated patients, one of ordinary skill in the art would have found it obvious to beneficially administer terlipressin taught by claim 1 of the ‘502 application to treat the pre-selected patients taught by the cited references.
Thus, claim 1 of the ‘502 application in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. are obvious to the instant claims 53-55, 58-76, and 78-82.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because applicant’s request of this rejection held in abeyance until rejections are overcomes does not overcome this rejection.
Claims 53-55, 58-76, and 78-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-10 of copending Application No. 17/976,606 (the ‘606 application, 1/9/2026) in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. (cited in the 2nd 103 rejection above).
Claim 9 of the ‘606 application disclosed administration of terlipressin to treat hepatorenal syndrome in an adult patient with baseline SpO2 ≥ 90%, MEDL score <35, ACLF grade < 3 and SCr < 5 mg/dL.
Claim 9 of the ‘606 application disclosed the composition comprising 1 mg terlipressin acetate and 10 mg mannitol.
Claims 9-10 of the ‘606 application dis not teach monitoring fluid overload during the treatment.
The relevancy of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. as applied to claims 53-55, 58-76, and 78-82 not repeated here.
Because Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach beneficial administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment and monitoring fluid overload and other adverse events during terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially administer terlipressin taught by claims 9-10 of the ‘606 application to treat the pre-selected patients taught by the cited references.
Thus, claims 9-10 of the ‘606 application in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. are obvious to the instant claims 53-55, 58-76, and 78-82.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because applicant’s request of this rejection held in abeyance until rejections are overcomes does not overcome this rejection.
Claims 53-55, 58-76, and 78-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32-33 of copending Application No. 18/416,231 (the ‘231 application, 1/23/2026) in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. (cited in the 2nd 103 rejection above).
Claim 32 of the ‘231 application disclosed a method of treating type-1 hepatorenal syndrome comprising administration of terlipressin to an adult patient with baseline SpO2 ≥ 90%, MEDL score <35, ACLF grade < 3 and SCr < 5 mg/dL.
Claim 33 of the ‘231 application disclosed the dosage of terlipressin is 1 mg of terlipressin acetate.
Claims 32-33 of the ‘231 application dis not teach monitoring fluid overload during the treatment.
The relevancy of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. as applied to claims 53-55, 58-76, and 78-82 not repeated here.
Because Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach beneficial administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment and monitoring fluid overload and other adverse events during terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially administer terlipressin taught by claims 32-33 of the ‘231 application to treat the pre-selected patients taught by the cited references.
Thus, claims 32-33 of the ‘231 application in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. are obvious to the instant claims 53-55, 58-76, and 78-82.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because applicant’s request of this rejection held in abeyance until rejections are overcomes does not overcome this rejection.
Claims 53-55, 58-76, and 78-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of copending Application No. 18/431,587 (the ‘587 application, 11/13/2025) in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. (cited in the 2nd 103 rejection above).
Claim 17 of the ‘587 application disclosed a method of treating type-1 hepatorenal syndrome comprising administration of terlipressin to an adult patient with baseline SpO2 ≥ 90%, MEDL score <35, ACLF grade < 3 and SCr < 5 mg/dL.
Claim 17 of the ‘587 application dis not teach monitoring fluid overload during the treatment.
The relevancy of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. as applied to claims 53-55, 58-76, and 78-82 not repeated here.
Because Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach beneficial administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment and monitoring fluid overload and other adverse events during terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially administer terlipressin taught by claim 17 of the ‘587 application to treat the pre-selected patients taught by the cited references.
Thus, claim 17 of the ‘587 application in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. are obvious to the instant claims 53-55, 58-76, and 78-82.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because applicant’s request of this rejection held in abeyance until rejections are overcomes does not overcome this rejection.
Claims 53-55, 58-76, and 78-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of copending Application No. 18/783,546 (the ‘546 application, 11/13/2025) in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. (cited in the 2nd 103 rejection above). The claim amendment of ‘546 application filed 1/20/2026 is non-compliance amendment; thus, this ODP rejection is based on the claims filed on 3/3/2025.
Claim 1 of the ‘546 application disclosed a method of treating type-1 hepatorenal syndrome comprising administration of terlipressin to an adult patient with baseline SpO2 ≥ 90%, MEDL score <35, and ACLF grade < 3.
Claim 2 of the ‘546 application disclosed continuously monitoring SpO2 during administration of the terlipressin.
Claims 1-2 of the ‘546 application do not teach patients with a baseline SCr < 5 mg/dL or monitoring fluid overload during the treatment.
The relevancy of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. as applied to claims 53-55, 58-76, and 78-82 not repeated here.
Because Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach beneficial administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment and monitoring fluid overload and other adverse events during terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially administer terlipressin taught by claims 1-2 of the ‘546 application to treat the pre-selected patients taught by the cited references.
Thus, claims 1-2 of the ‘546 application in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. are obvious to the instant claims 53-55, 58-76, and 78-82.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because applicant’s request of this rejection held in abeyance until rejections are overcomes does not overcome this rejection.
Claims 53-55, 58-76, and 78-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 13 of copending Application No. 18/783,572 (the ‘572 application, 11/13/2025) in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. (cited in the 2nd 103 rejection above).
Claim 13 of the ‘572 application disclosed administration of terlipressin to treat hepatorenal syndrome in an adult patient with baseline SpO2 ≥ 90%, MEDL score <35, ACLF grade < 3.
Claim 13 of the ‘572 application does not teach patients with a baseline SCr < 5 mg/dL or monitoring fluid overload during the treatment.
The relevancy of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. as applied to claims 53-55, 58-76, and 78-82 not repeated here.
Because Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach beneficial administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment and monitoring fluid overload and other adverse events during terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially administer terlipressin taught by claim 13 of the ‘572 application to treat the pre-selected patients taught by the cited references.
Thus, claim 13 of the ‘572 application in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. are obvious to the instant claims 53-55, 58-76, and 78-82.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because applicant’s request of this rejection held in abeyance until rejections are overcomes does not overcome this rejection.
Claims 53-55, 58-76, and 78-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22 and 28 of copending Application No. 19/213,363 (the ‘363 application, 12/22/2025) in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. (cited in the 2nd 103 rejection above).
Claim 22 of the ‘363 application disclosed administration of terlipressin to treat hepatorenal syndrome in an adult patient with baseline MEDL score <35, ACLF grade < 3, and SCr < 5 mg/dL.
Claim 28 of the ‘363 application disclosed the dosage of administered terlipressin comprising 0.85 mg of terlipressin or 1mg of terlipressin acetate.
Claims 22 and 28 of the ‘363 application did not teach patients with a baseline SpO2 ≥ 90% or monitoring fluid overload during the treatment.
The relevancy of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. as applied to claims 53-55, 58-76, and 78-82 not repeated here.
Because Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach beneficial administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment and monitoring fluid overload and other adverse events during terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially administer terlipressin taught by claims 22 and 28 of the ‘363 application to treat the pre-selected patients taught by the cited references.
Thus, claims 22 and 28 of the ‘363 application in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. are obvious to the instant claims 53-55, 58-76, and 78-82.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because applicant’s request of this rejection held in abeyance until rejections are overcomes does not overcome this rejection.
Claims 53-55, 58-76, and 78-82 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, 6/20/2025) in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. (cited in the 2nd 103 rejection above).
Claim 1 of the ‘769 application disclosed a formulation of terlipressin acetate.
Claim 1 of the ‘769 application does not teach administration of terlipressin to treat a patient with hepatorenal syndrome.
The relevancy of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. as applied to claims 53-55, 58-76, and 78-82 not repeated here.
Because Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach beneficial administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment and monitoring fluid overload and other adverse events during terlipressin treatment with 1 mg terlipressin acetate (See NCT02770716 p7, Assigned Interventions), one of ordinary skill in the art would have found it obvious to beneficially administer terlipressin taught by claim 1 of the ‘769 application to treat the pre-selected patients taught by the cited references.
Thus, claim 1 of the ‘769 application in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. are obvious to the instant claims 53-55, 58-76, and 78-82.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because applicant’s request of this rejection held in abeyance until rejections are overcomes does not overcome this rejection.
Claims 53-55, 58-76, and 78-82 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, 6/20/2025) in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. (cited in the 2nd 103 rejection above).
Claim 1 of the ‘777 application disclosed a formulation of terlipressin acetate.
Claim 1 of the ‘777 application does not teach administration of terlipressin to treat a patient with hepatorenal syndrome.
The relevancy of Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. as applied to claims 53-55, 58-76, and 78-82 not repeated here.
Because Jamail et al. in view of Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. teach beneficial administration of terlipressin to a pre-selected patient group likely to respond to terlipressin treatment and monitoring fluid overload and other adverse events during terlipressin treatment with 1 mg terlipressin acetate (See NCT02770716 p7, Assigned Interventions), one of ordinary skill in the art would have found it obvious to beneficially administer terlipressin taught by claim 1 of the ‘769 application to treat the pre-selected patients taught by the cited references.
Thus, claim 1 of the ‘777 application in view of Jamail et al., Lucassin, Wisniewski et al., Alwadhi et al., Ling et al., Alessandria et al., Rodriguez et al., Bota et al., NCT02770716, and Boyer et al. are obvious to the instant claims 53-55, 58-76, and 78-82.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 1/15/2026 have been fully considered but they are not persuasive because applicant’s request of this rejection held in abeyance until rejections are overcomes does not overcome this rejection.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/J.L/Examiner, Art Unit 1658
15-March-2026
/LI N KOMATSU/ Primary Examiner, Art Unit 1658