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 28-47 are pending.
Claims 1-27 are cancelled.
NEW Claims 28-47 have been examined.
Priority
This application is a CIP 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
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Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/24/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Withdrawn Rejection
All rejections of record are withdrawn because the new claims overcome the rejection of record.
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 28-36 and 39-47 are rejected under 35 U.S.C. 103 as being unpatentable over Jamil et al. (US 2016/0113994 A1, cited 9/24/2025) in view of (A) Boyer et al. (Journal of Hepatology. 2011; 55: 315-321, cited , cited 9/24/2025) for teaching SCr level, (B) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, cited , cited 9/24/2025) for teaching ACLF grade, (C) Ling et al. (Sci Rep. 2017; 7: 42253) in view of Alexandria et al. (Hepatology. 2005;41:1282-1289) for teaching MELD score, (D) Lucassin (Ikaria, Inc. 2012, previously , cited 7/11/2025) in view of Wisniewski et al. (US 2016/0122386 A1, cited 7/11/2025), Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734, cited 9/24/2025), and Bota et al. (The Journal of Emergency Medicine, Vol 13, No 3, pp 305- JIJ , 1995, cited 9/24/2025) for teaching SpO2 level, and (E) NCT02770716 (ver 13: 2018-08-09, cited 9/24/2025) and evidenced by Terlivaz® (Terlipressin product. revised:04/2023, cited 9/24/2025) for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response .
Claim 28 is drawn to a method of improving survival in a patient having type 1 hepatorenal syndrome (HRS-1), the method comprising:
a) obtaining a baseline serum creatinine (SCr) level < 5 mg/dl in the patient;
b) obtaining a baseline acute-on-chronic liver failure (ACLF) grade< 3 in the patient;
c) obtaining a baseline model end stage liver disease (MELD) score < 35 in the patient;
d) obtaining a baseline oxygen saturation (SpO2) ≥ 90 % in the patient; and
e) administering a pharmaceutical composition comprising 1 mg of terlipressin acetate to the patient every 6 hours for up to 14 days;
f) wherein the patient does not have ongoing coronary, peripheral or mesenteric ischemia, or has a history of severe cardiovascular conditions, cerebrovascular and ischemic disease;
g) wherein the median Cmax of terlipressin is about 70.5 ng/mL after administration of the pharmaceutical composition;
h) wherein after administration of the pharmaceutical composition, the patient experiences an increase in diastolic, systolic, and mean arterial pressure (MAP) and a decrease in heart rate within 5 minutes.
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 pre-selected patients expected to be beneficial and even life-saving with terlipressin as well as (b) reduce the incidence of adverse events in patients administered with terlipressin by excluding patients unlikely to respond to terlipressin treatment.
With respect to obtaining a baseline serum creatinine (SCr) level of step (a), 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 to a selected patient with baseline of SCr < 5.0 mg/dl.
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With respect to obtaining a baseline acute-on-chronic liver failure (ACLF) grade< 3 of step (b), 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 as follows (p958, col 2, Table 1). 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.
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With respect to obtaining a baseline model end stage liver disease (MELD) score < 35 of step (c), Ling et al. teach MELD has been validated as a good predictor of mortality for a broader range of patients with end-stage liver disease, including candidates on the waiting list for liver transplantation (p1, para 2). 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 above (p5, Fig 2B). 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 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 shown as follows (p1285, Fig 4). The lower MELD score (< 35) has a higher 3-month survival probability consistent with Ling et al. Thus, one of 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.
With respect to obtaining a baseline oxygen saturation (SpO2) ≥ 90 % of step (d), Lucassin teaches Lucassin formulation contains 0.85 mg terlipressin free base in acetate salt as a sterile, lyophilized powder for intravenous administration (p1, Description), reading on terlipressin acetate. Lucassin 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), consistent with Jamil et al. [0022]. Common adverse events of terlipressin including fluid overload can be found in Lucassin’s Table 2 (p8), Table 3 (p9), and Table 4 (p10). Lucassin explicitly 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. 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), one of ordinary skill in the art would have found it obvious to obtain the baseline of SpO2 and only administer terlipressin to a patient with baseline SpO2 ≥ 90% to avoid administration of terlipressin to a patient with hypoxia or at risk of developing ischaemic events. Since ischaemia or hypoxia is a known adverse event resulting from continuous terlipressin treatment, one of ordinary skill in the art would have found it obvious to constantly monitor SpO2 with Bota’s continuous pulse oximetry before and/or after each administration of terlipressin to further avoid administration of terlipressin to a patient with hypoxia or at risk of developing ischaemic events.
With respect to step (e), Lucassin teaches Lucassin formulation is provided as lyophilized powder comprising 0.85 mg terlipressin together with mannitol and acetate salt in a vial. Lucassin teaches each vial must be reconstituted with 5ml of 0.9% sodium chloride injection prior to use (p1, Description). Lucassin teaches the recommended starting dose is one vial of LUCASSIN (0.85 mg terlipressin) every 6 hours by slow intravenous bolus injection for a period of up to 14 days (p3, para 1 ). Similarly, NCT02770716 teaches 1 mg lyophilized terlipressin acetate and 10 mg mannitol (11 mg mannitol without terlipressin acetate for placebo) reconstituted with 5 ml of sterile sodium chloride solution for IV bolus injection every 6 hours consistent with Lucassin’s teachings (p7, Arms and Interventions). NCT02770716 further teaches HRS Reversal measured with 2 consecutive SCr values ≤ 1.5 mg/dl at least 2 hours apart up to 14 days (p7, Primary Outcome Measures). Terlivaz is cited as evidence to show inherent properties of terlipressin taught by Lucassin and NCT02770716. Each vial of Terlivaz contains 0.85 mg terlipressin in acetate salt and mannitol (taught by Lucassin), equivalent to 1 mg terlipressin acetate and 10.0 mg mannitol (taught by NCT02770716). Lucassin and NCT02770716 are teaching the same terlipressin with acetate salt illustrated by Terlivaz; thus, Lucassin in view of NCT02770716 and evidenced by Terlivaz meet the limitation of step (e).
With respect to the wherein (f), Jamil et al. teach ischemic events (cardiac, gastrointestinal, and skin) can occur following administration of terlipressin and may require temporary interruption, dose decrease, or permanent discontinuation [0022], consistent with Lucassin’s teaching (p6, Ischaemic Events). Furthermore, exclusion of a patient with SpO2 < 90% from terlipressin reads on the patient does not have ongoing coronary, peripheral or mesenteric ischemia.
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With respect to the wherein (g), Lucassin teaches Lucassin is provided as lyophilized powder comprising 0.85 mg terlipressin together with mannitol and acetate salt in a vial. Lucassin teaches each vial must be reconstituted with 5ml of 0.9% sodium chloride injection prior to use (p1, Description). 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) same conditions recommended by Terlivaz (p1, col 1, Recommended Dosage Regimen: 2.2 and p2, col 1, Fig 1: dosing chart shown as follows). NCT02770716 teaches 1 mg lyophilized terlipressin acetate and 10 mg mannitol (11 mg mannitol without terlipressin acetate for placebo) reconstituted with 5 ml of sterile sodium chloride solution for IV bolus injection every 6 hours consistent with Lucassin’s teachings (p7, Arms and Interventions). Terlivaz is cited as evidence to show that each vial contains 0.85 mg terlipressin, equivalent to 1 mg terlipressin acetate and 10.0 mg mannitol as taught by Lucassin in view of NCT02770716. Since the terlipressin acetate salt formulation taught by Lucassin in view of NCT02770716 is the same formulation as Terlivaz and the route of administered terlipressin is via the same slow intravenous bolus injection (Lucassin, p11, DOSAGE AND ADMINISTRATION; Terlivaz, p2, col 1, 2.3 Recommended Dosage), the prior art terlipressin formulation must have the same pharmacokinetic parameter of Cmax. Terlivaz is cited as evidence to show the median Cmax of terlipressin is about 70.5 ng/mL after administration of the pharmaceutical composition under the prior art conditions (p3, col 2, 12.3 Pharmacokinetics). MPEP 2112.01 (II) states "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
With respect to the wherein (h), Lucassin teaches Terlipressin increases mean arterial pressure (MAP) and decreases heart rate while increasing systemic vascular resistance, reading on increase in diastolic and systolic pressure, (p2, Pharmacodynamics). Terlivaz is cited as evidence to show a patient’s response “After administration of a single 0.85 mg dose of terlipressin in patients with hepatorenal syndrome type 1 (HRS-1), an increase in the diastolic, systolic, and mean arterial pressure (MAP), and decrease in heart rate were evident within 5 minutes after dosing and were maintained for at least 6 hours after dosing (p3, col 2, 12.2 Pharmacodynamics). Also see MPEP 2112.01 (II) states "Products of identical chemical composition cannot have mutually exclusive properties."
One of ordinary skill in the art before the effective fining date of this invention would have found it obvious to combine Jamil et al. with (A) Boyer et al., (B) Rodriguez et al. and (C) Ling et al. in view of Alexandria et al. because Jamil et al. teach (i) identify a patient likely to respond to terlipressin and only treat those pre-selected patients expected to be beneficial and even life-saving with terlipressin as well as (ii) reduce the incidence of adverse events in patients administered with terlipressin by excluding patients unlikely to respond to terlipressin treatment, and (A) 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), (B) 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 in Table 1 (p958, col 2), and (C) Ling et al. teach MELD has been validated as a good predictor of mortality for a broader range of patients with end-stage liver disease, including candidates on the waiting list for liver transplantation (p1, para 2) and Ling et al. show MELD with great correlation with 3-month death, the lower MELD score the better (p5, Fig 3). 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 shown as follows (p1285, Fig 4). The lower MELD score (< 35) has a higher 3-month survival probability consistent with Ling et al. The combination would have reasonable expectation of success because all references suggest a diagnostic measure relevant to HRS-1 patient selection likely to respond to terlipressin treatment able to improve survival of treated patients.
With respect to claims 29-30, Terlivaz is cited as evidence to show intrinsic properties of pharmacokinetic parameters of administered terlipressin at 0.85 mg (equivalent to 1 mg terlipressin acetate) via IV bolus injection comprising (i) AUC24h of 123ng*hr/mL and (ii) Cave of 14.2 ng/mL (p3, col 2, 12.3 Pharmacokinetics).
With respect to claims 31-33, Terlivaz is cited as evidence to show intrinsic properties of pharmacodynamic parameters of administered terlipressin at 0.85 mg (equivalent to 1 mg terlipressin acetate) via IV bolus injection comprising (i) maximum change in blood pressure and heart rate occurred at 1.2 to 2 hours post dose, (ii) maximum effect MAP was an increase of 16.2 mmHg, and (iii) maximum effect for heart rate was a decrease of 10.6 beats/minute (p3, 12.2 Pharmacodynamics).
With respect to claim 34, Terlivaz is cited as evidence to show intrinsic properties of the clearance of terlipressin was 27.4 L/hr (p4, col 1, Elimination).
With respect to claim 35, Jamil et al. teach the treatment method further comprising administering albumin [0036] consistent with Lucassin (p3, para 1).
With respect to claim 36, Lucassin teaches management of suspected adverse drug reactions may require temporary interruption (reading on discontinue terlipressin treatment) and/or dose reduction (p11, DOSAGE AND ADMINISTRATION, para 3). Lucassin shows fluid overload is one of common adverse event of terlipressin (p8, Table 2; p9, Table 3). Thus, one of ordinary would have found it obvious to discontinue terlipressin treatment after developing fluid overload.
With respect to claim 39, the rejection of steps (a)-(d) are the same reasons in rejection of the base claim 28 described above.
Regarding steps (e) and (f), Lucassin teaches serum creatinine levels should be monitored daily to assess response to therapy (p6, Laboratory Monitoring). 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) 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 (Lucassin, p11, DOSAGE AND ADMINISTRATION, para 1).
Regarding step (g), Lucassin teaches terlipressin treatment success at Day 14 (two serum creatinine [SCr] levels ≤ 132.6 μmol/L 48 ± 24 h apart without intervening (p3, para 2). Furthermore, NCT02770716 further teaches HRS Reversal measured with 2 consecutive SCr values ≤ 1.5 mg/dl at least 2 hours apart up to 14 days (p7, Primary Outcome Measures).
Regarding the first 3 wherein clauses in claim 39, Terlivaz is cited as evidence to show intrinsic properties of pharmacodynamic and Pharmacokinetic parameters of administered terlipressin at 0.85 mg (equivalent to 1 mg terlipressin acetate) via IV bolus injection (Terlivaz, p3, col 2, 12.2 Pharmacodynamics and 12.3 Pharmacokinetics).
Regarding the 4th to 6th wherein clauses in claim 39, Lucassin teaches Lucassin is provided as lyophilized powder comprising 0.85 mg terlipressin together with mannitol and acetate salt in a vial, reading on a single dose, (p1, Description). Lucassin teaches reconstituting each vial with 5 ml of sterile 0.9% sodium chloride injection prior to administration. If not administered immediately, the reconstituted solution should be refrigerated (2 - 8°C) up to 24 hrs prior to use (p11, Instructions for IV Administration).
With respect to claim 40, 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).
With respect to claim 41, Jamil et al. show the patient's SCr level is measured 4 days after
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administration of the composition is started and discontinue terlipressin treatment if SCr is at or above the baseline SCr level without reduction in SCr on day 4 shown as follows (Fig 1).
With respect claims 42-44, Lucassin teaches if serum creatinine (SCr) 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 (Lucassin, p11, DOSAGE AND ADMINISTRATION, para 1), consistent with Jamil et al. [0098].
With respect to claim 45, Lucassin teaches due to its constrictive effects on smooth muscle, terlipressin should be used with caution in patients with severe asthma or chronic obstructive pulmonary disease (COPD). Patients with these disorders who require terlipressin should be closely monitored and any bronchospasm should be treated symptomatically (p6, Respiratory Effects), consistent with Jamil et al. [0022]. Lucassin show respiratory failure is one of common adverse event of terlipressin treatment (p8, Table 2). 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). 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).
With respect to claims 46-47, 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). Jamil et al. teach administration of terlipressin ranged from 0.5 mg to 2 mg as a slow bolus injection over 2 minutes [0146].
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
2. Claims 28-37 and 39-47 are rejected under 35 U.S.C. 103 as being unpatentable over Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® as applied to claims 28-36, 39-47 and further in view of Pulimood et al. (Crit Care 2000, 4:151–155).
Claim 37 is drawn to the patient experiences fluid overload and administration of albumin is discontinued.
The cited references of Jamail et al. in view of cited references (A)-(E) teach fluid overload as an adverse event of terlipressin (See Lucassin p8-Table 2; p9-Table 3; p10-Table 4).
Jamail et al. in view of cited references (A)-(E) did not specify discontinuation of albumin administration to patients with fluid overload.
Pulimood et al. teach administration of albumin there is up to a fourfold increase in volume retention, which can result in fluid overload, especially pulmonary oedema (p3, col 1, para 2). Because albumin increases volume retention and results in fluid overload, one of ordinary skill in the art would have found it obvious to discontinue administration of albumin in a patient developing fluid overload.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® with Pulimood’s teaching of albumin because (1) Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® teach administration of terlipressin and albumin to treat a selected patient group likely to respond to terlipressin treatment and (2) Pulimood et al. teach administration of albumin there is up to a fourfold increase in volume retention, which can result in fluid overload, especially pulmonary oedema (p3, col 1, para 2). The combination would have reasonable expectation of success because discontinuation of albumin administration will eliminate albumin-mediated fluid overload in the treated patients.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
3. Claims 28-36 and 38-47 are rejected under 35 U.S.C. 103 as being unpatentable over Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® as applied to claims 28-36, 39-47 and further in view of Mcpherson et al. (WO 2018/208684).
Claim 38 is drawn to administration of diuretics to the patient experiences fluid overload.
The cited references of Jamail et al. in view of cited references (A)-(E) teach fluid overload as an adverse event of terlipressin (See Lucassin p8-Table 2; p9-Table 3; p10-Table 4).
Jamail et al. in view of cited references (A)-(E) did not specify administration of diuretics to patients with fluid overload.
Mcpherson et al. teach hospitalized fluid overload patients are typically treated with IV diuretics and the loop diuretic furosemide is the most frequently prescribed diuretic for treatment of volume overload [0085]. Since diuretics, such as loop diuretic furosemide, are commonly used to treat patients with fluid overload, one of ordinary skill in the art would have found it obvious to administer diuretics (e.g., furosemide) to treat fluid overload in patients.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® with Mcpherson’s teaching of diuretics because (1) Jamil et al. and Lucassin teach fluid overload as an adverse events of terlipressin treatment and (2) Mcpherson et al. teach hospitalized fluid overload patients are typically treated with IV diuretics and the loop diuretic furosemide is the most frequently prescribed diuretic for treatment of volume overload [0085]. The combination would have reasonable expectation of success because diuretics (e.g., furosemide) is are commonly used to treat patients with fluid overload taught by Mcpherson et al. [0085].
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
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 28-36 and 39-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 9, and 12 of U.S. Patent No. 10,335,452 B2 (the ‘452 patent) in view of Jamil et al. (US 2016/0113994 A1, cited 9/24/2025) in view of (A) Boyer et al. (Journal of Hepatology. 2011; 55: 315-321, cited , cited 9/24/2025) for teaching SCr level, (B) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, cited , cited 9/24/2025) for teaching ACLF grade, (C) Ling et al. (Sci Rep. 2017; 7: 42253) in view of Alexandria et al. (Hepatology. 2005;41:1282-1289) for teaching MELD score, (D) Lucassin (Ikaria, Inc. 2012, previously , cited 7/11/2025) in view of Wisniewski et al. (US 2016/0122386 A1, cited 7/11/2025), Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734, cited 9/24/2025), and Bota et al. (The Journal of Emergency Medicine, Vol 13, No 3, pp 305- JIJ , 1995, cited 9/24/2025) for teaching SpO2 level, and (E) NCT02770716 (ver 13: 2018-08-09, cited 9/24/2025) and evidenced by Terlivaz® (Terlipressin product. revised:04/2023, cited 9/24/2025) for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response .
Claim 1 of the ‘452 patent disclosed a method of treating type 1 hepatorenal syndrome comprising administering terlipressin.
Claim 6 of the ‘452 patent disclosed terlipressin administered to a patient in the range of about 0.5 mg to about 2.0 mg every 4 to 6 hours .
Claim 9 of the ‘452 patent disclosed continuing administration of terlipressin to the patient for an additional 3 to 12 days if the patient has a reduction in serum creatinine level during the initial 1 to 4 days of terlipressin administration.
Claim 12 of the ‘452 patent disclosed administration of terlipressin to the patient resulting in reversal of one or more complication factors.
Claims 1, 6, 9, and 12 of the ‘452 patent do not teach obtaining a baseline of SpO2 or ACLF grade in a patient.
The relevancy of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response as applied to claims 28-36 and 39-47 is described above not repeated here.
Because Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® determining and treating a patient likely to respond to terlipressin (terlipressin is known to be effective in only 33-60% of HRS-1 patients) to beneficially enhance a method of administering terlipressin acetate to treat a patient with hepatorenal syndrome, one of ordinary skill in the art would have found it obvious to combine claims 1, 6, 9, and 12 of the ‘452 patent with Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
Thus, claims 1, 6, 9, and 12 of the ‘452 patent in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® are obvious to the instant claims 28-36 and 39-47.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
Claims 28-36 and 39-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44 and 53 of copending Application No. 17/104,864 (the ‘864 application of 2/17/2026) in view of Jamil et al. (US 2016/0113994 A1, cited 9/24/2025) in view of (A) Boyer et al. (Journal of Hepatology. 2011; 55: 315-321, cited , cited 9/24/2025) for teaching SCr level, (B) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, cited , cited 9/24/2025) for teaching ACLF grade, (C) Ling et al. (Sci Rep. 2017; 7: 42253) in view of Alexandria et al. (Hepatology. 2005;41:1282-1289) for teaching MELD score, (D) Lucassin (Ikaria, Inc. 2012, previously , cited 7/11/2025) in view of Wisniewski et al. (US 2016/0122386 A1, cited 7/11/2025), Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734, cited 9/24/2025), and Bota et al. (The Journal of Emergency Medicine, Vol 13, No 3, pp 305- JIJ , 1995, cited 9/24/2025) for teaching SpO2 level, and (E) NCT02770716 (ver 13: 2018-08-09, cited 9/24/2025) and evidenced by Terlivaz® (Terlipressin product. revised:04/2023, cited 9/24/2025) for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response .
Claims 44 and 53 of the ‘864 application disclosed a method of administering terlipressin to a selected patient group with a serum creatinine (SCr) level< 5 mg/dl and an acute-on-chronic liver failure (ACLF) grade < 3 to improve survival of a patient with terlipressin treatment.
Claims 44 and 53 of the ‘864 application did not disclose the selected patient with model end stage liver disease (MELD) score < 35 or oxygen saturation (SpO2) ≥ 90 %.
The relevancy of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response as applied to claims 28-36 and 39-47 is described above not repeated here.
Because Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® teach a patient’s baseline MELD score < 35 and oxygen saturation of SpO2 ≥ 90 % likely response to terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially combine claims 44 and 53 of the ‘864 application with Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
Thus, claims 44 and 53 of the ‘864 application in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® are obvious to the instant claims 28-36 and 39-47.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
Claims 28-36 and 39-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 53 of copending Application No. 17/340,765 (the ‘765 application of 1/15/2026) in view of Jamil et al. (US 2016/0113994 A1, cited 9/24/2025) in view of (A) Boyer et al. (Journal of Hepatology. 2011; 55: 315-321, cited , cited 9/24/2025) for teaching SCr level, (B) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, cited , cited 9/24/2025) for teaching ACLF grade, (C) Ling et al. (Sci Rep. 2017; 7: 42253) in view of Alexandria et al. (Hepatology. 2005;41:1282-1289) for teaching MELD score, (D) Lucassin (Ikaria, Inc. 2012, previously , cited 7/11/2025) in view of Wisniewski et al. (US 2016/0122386 A1, cited 7/11/2025), Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734, cited 9/24/2025), and Bota et al. (The Journal of Emergency Medicine, Vol 13, No 3, pp 305- JIJ , 1995, cited 9/24/2025) for teaching SpO2 level, and (E) NCT02770716 (ver 13: 2018-08-09, cited 9/24/2025) and evidenced by Terlivaz® (Terlipressin product. revised:04/2023, cited 9/24/2025) for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response .
Claim 53 of the ‘765 application disclosed a method of administering terlipressin to a selected patient group with a baseline model end stage liver disease (MELD) score < 35, oxygen saturation (SpO2) ≥ 90 % and an acute-on-chronic liver failure (ACLF) grade < 3 to improve survival of a patient with terlipressin treatment.
Claim 53 of the ‘765 application did not disclose the selected patient with a serum creatinine (SCr) level< 5 mg/dl.
The relevancy of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response as applied to claims 28-36 and 39-47 is described above not repeated here.
Because Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® teach a patient’s baseline serum creatinine (SCr) level< 5 mg/dl likely response to terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially combine claim 53 of the ‘765 application with Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
Thus, claim 53 of the ‘765 application in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® are obvious to the instant claims 28-36 and 39-47.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
Claims 28-36 and 39-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/587,442 (the ‘442 application of 9/30/2025) in view of Jamil et al. (US 2016/0113994 A1, cited 9/24/2025) in view of (A) Boyer et al. (Journal of Hepatology. 2011; 55: 315-321, cited , cited 9/24/2025) for teaching SCr level, (B) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, cited , cited 9/24/2025) for teaching ACLF grade, (C) Ling et al. (Sci Rep. 2017; 7: 42253) in view of Alexandria et al. (Hepatology. 2005;41:1282-1289) for teaching MELD score, (D) Lucassin (Ikaria, Inc. 2012, previously, cited 7/11/2025) in view of Wisniewski et al. (US 2016/0122386 A1, cited 7/11/2025), Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734, cited 9/24/2025), and Bota et al. (The Journal of Emergency Medicine, Vol 13, No 3, pp 305- JIJ , 1995, cited 9/24/2025) for teaching SpO2 level, and (E) NCT02770716 (ver 13: 2018-08-09, cited 9/24/2025) and evidenced by Terlivaz® (Terlipressin product. revised:04/2023, cited 9/24/2025) for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response .
Claim 1 of the ‘442 application disclosed a method of administering terlipressin to a selected patient group likely to response to terlipressin treatment and discontinuing terlipressin administration if the serum creatinine level is at or above the baseline value after day 4.
Claim 1 of the ‘442 application dis not specify selection of a patient group likely to respond to terlipressin treatment based on baseline values of MEDL, ACLF, or SpO2.
The relevancy of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response as applied to claims 28-36 and 39-47 is described above not repeated here.
Because Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® teach a patient’s baseline MELD score < 35, oxygen saturation of SpO2 ≥ 90%, ACLF grade < 3, and (SCr) level< 5 mg/dl likely response to terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially combine claim 1 of the ‘442 application with Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
Thus, claim 1 of the ‘442 application in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® are obvious to the instant claims 28-36 and 39-47.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
Claims 28-36 and 39-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/976,606 (the ‘606 application of 1/9/2026) in view of Jamil et al. (US 2016/0113994 A1, cited 9/24/2025) in view of (A) Boyer et al. (Journal of Hepatology. 2011; 55: 315-321, cited , cited 9/24/2025) for teaching SCr level, (B) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, cited , cited 9/24/2025) for teaching ACLF grade, (C) Ling et al. (Sci Rep. 2017; 7: 42253) in view of Alexandria et al. (Hepatology. 2005;41:1282-1289) for teaching MELD score, (D) Lucassin (Ikaria, Inc. 2012, previously, cited 7/11/2025) in view of Wisniewski et al. (US 2016/0122386 A1, cited 7/11/2025), Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734, cited 9/24/2025), and Bota et al. (The Journal of Emergency Medicine, Vol 13, No 3, pp 305- JIJ , 1995, cited 9/24/2025) for teaching SpO2 level, and (E) NCT02770716 (ver 13: 2018-08-09, cited 9/24/2025) and evidenced by Terlivaz® (Terlipressin product. revised:04/2023, cited 9/24/2025) for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response .
Claim 9 the ‘606 application disclosed a method of administering terlipressin to a selected patient group for improving kidney function in an adult patient with type-1 hepatorenal syndrome.
Claim 9 the ‘606 application did not teach a dosage of terlipressin and pharmacokinetic or pharmacodynamic parameters.
The relevancy of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response as applied to claims 28-36 and 39-47 is described above not repeated here.
Because Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® teach an effective dosage of administered terlipressin and pharmacokinetic or pharmacodynamic parameters in patients associated with the administered dosage of terlipressin, one of ordinary skill in the art would have found it obvious to beneficially combine claim 9 the ‘606 application with Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
Thus, claim 9 of the ‘606 application in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® are obvious to the instant claims 28-36 and 39-47.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
Claims 28-36 and 39-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 32 of copending Application No. 18/416,231 (the ‘231 application of 1/23/2026) in view of Jamil et al. (US 2016/0113994 A1, cited 9/24/2025) in view of (A) Boyer et al. (Journal of Hepatology. 2011; 55: 315-321, cited , cited 9/24/2025) for teaching SCr level, (B) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, cited , cited 9/24/2025) for teaching ACLF grade, (C) Ling et al. (Sci Rep. 2017; 7: 42253) in view of Alexandria et al. (Hepatology. 2005;41:1282-1289) for teaching MELD score, (D) Lucassin (Ikaria, Inc. 2012, previously, cited 7/11/2025) in view of Wisniewski et al. (US 2016/0122386 A1, cited 7/11/2025), Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734, cited 9/24/2025), and Bota et al. (The Journal of Emergency Medicine, Vol 13, No 3, pp 305- JIJ , 1995, cited 9/24/2025) for teaching SpO2 level, and (E) NCT02770716 (ver 13: 2018-08-09, cited 9/24/2025) and evidenced by Terlivaz® (Terlipressin product. revised:04/2023, cited 9/24/2025) for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response .
Claim 32 the ‘231 application disclosed a method of administering terlipressin to a selected patient group for improving kidney function in an adult patient with type-1 hepatorenal syndrome.
Claim 32 the ‘231 application did not teach a dosage of terlipressin and pharmacokinetic or pharmacodynamic parameters.
The relevancy of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response as applied to claims 28-36 and 39-47 is described above not repeated here.
Because Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® teach an effective dosage of administered terlipressin and pharmacokinetic or pharmacodynamic parameters in patients associated with the administered dosage of terlipressin, one of ordinary skill in the art would have found it obvious to beneficially combine claim 32 the ‘231 application with Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
Thus, claim 32 the ‘231 application in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® are obvious to the instant claims 28-36 and 39-47.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
Claims 28-36 and 39-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of copending Application No. 18/431,587 (the ‘587 application of 10/13/2025) in view of Jamil et al. (US 2016/0113994 A1, cited 9/24/2025) in view of (A) Boyer et al. (Journal of Hepatology. 2011; 55: 315-321, cited , cited 9/24/2025) for teaching SCr level, (B) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, cited , cited 9/24/2025) for teaching ACLF grade, (C) Ling et al. (Sci Rep. 2017; 7: 42253) in view of Alexandria et al. (Hepatology. 2005;41:1282-1289) for teaching MELD score, (D) Lucassin (Ikaria, Inc. 2012, previously , cited 7/11/2025) in view of Wisniewski et al. (US 2016/0122386 A1, cited 7/11/2025), Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734, cited 9/24/2025), and Bota et al. (The Journal of Emergency Medicine, Vol 13, No 3, pp 305- JIJ , 1995, cited 9/24/2025) for teaching SpO2 level, and (E) NCT02770716 (ver 13: 2018-08-09, cited 9/24/2025) and evidenced by Terlivaz® (Terlipressin product. revised:04/2023, cited 9/24/2025) for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response .
Claim 17 of the ‘587 application disclosed a method of administering terlipressin to a selected patient group with a baseline model end stage liver disease (MELD) score < 35, serum creatinine (SCr) level< 5 mg/dl, and an acute-on-chronic liver failure (ACLF) grade < 3 to improve survival of a patient with terlipressin treatment.
Claim 17 of the ‘587 application did not disclose the selected patient with oxygen saturation (SpO2) ≥ 90%.
The relevancy of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response as applied to claims 28-36 and 39-47 is described above not repeated here.
Because Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® teach a patient’s baseline oxygen saturation (SpO2) ≥ 90% likely response to terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially combine claim 17 of the ‘587 application with Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
Thus, claim 17 of the ‘587 application in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® are obvious to the instant claims 28-36 and 39-47.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
Claims 28-36 and 39-47 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 of 3/3/2025) in view of Jamil et al. (US 2016/0113994 A1, cited 9/24/2025) in view of (A) Boyer et al. (Journal of Hepatology. 2011; 55: 315-321, cited , cited 9/24/2025) for teaching SCr level, (B) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, cited , cited 9/24/2025) for teaching ACLF grade, (C) Ling et al. (Sci Rep. 2017; 7: 42253) in view of Alexandria et al. (Hepatology. 2005;41:1282-1289) for teaching MELD score, (D) Lucassin (Ikaria, Inc. 2012, previously , cited 7/11/2025) in view of Wisniewski et al. (US 2016/0122386 A1, cited 7/11/2025), Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734, cited 9/24/2025), and Bota et al. (The Journal of Emergency Medicine, Vol 13, No 3, pp 305- JIJ , 1995, cited 9/24/2025) for teaching SpO2 level, and (E) NCT02770716 (ver 13: 2018-08-09, cited 9/24/2025) and evidenced by Terlivaz® (Terlipressin product. revised:04/2023, cited 9/24/2025) for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response .
Examiner’s Note:
The ‘546 application has non-compliance of claim amendment in filing RCE; thus, the claims under ODP rejection was filed 3/3/2025 NOT the non-compliance of claim amendment filed on 1/20/2026.
Claim 1 of the ‘546 application disclosed a method of treating an adult patient with hepatorenal syndrome comprising steps as follows.
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Claim 2 of the ‘546 application disclosed SpO2 is monitored continuously during administration of the terlipressin.
Claims 1-2 the ‘546 application did not disclose a dosage of terlipressin and pharmacokinetic or pharmacodynamic parameters.
The relevancy of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response as applied to claims 28-36 and 39-47 is described above not repeated here.
Because Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® teach an effective dosage of administered terlipressin and pharmacokinetic or pharmacodynamic parameters in patients associated with the administered dosage of terlipressin, one of ordinary skill in the art would have found it obvious to beneficially combine claims 1-2 the ‘546 application with Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
Thus, claims 1-2 the ‘546 application in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® are obvious to the instant claims 28-36 and 39-47.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
Claims 28-36 and 39-47 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 of 10/23/2025) in view of Jamil et al. (US 2016/0113994 A1, cited 9/24/2025) in view of (A) Boyer et al. (Journal of Hepatology. 2011; 55: 315-321, cited , cited 9/24/2025) for teaching SCr level, (B) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, cited , cited 9/24/2025) for teaching ACLF grade, (C) Ling et al. (Sci Rep. 2017; 7: 42253) in view of Alexandria et al. (Hepatology. 2005;41:1282-1289) for teaching MELD score, (D) Lucassin (Ikaria, Inc. 2012, previously , cited 7/11/2025) in view of Wisniewski et al. (US 2016/0122386 A1, cited 7/11/2025), Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734, cited 9/24/2025), and Bota et al. (The Journal of Emergency Medicine, Vol 13, No 3, pp 305- JIJ , 1995, cited 9/24/2025) for teaching SpO2 level, and (E) NCT02770716 (ver 13: 2018-08-09, cited 9/24/2025) and evidenced by Terlivaz® (Terlipressin product. revised:04/2023, cited 9/24/2025) for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response .
Claim 13 of the ‘572 application disclosed a method of administering terlipressin to a selected patient group with a baseline model end stage liver disease (MELD) score < 35, serum creatinine (SCr) level< 5 mg/dl, an acute-on-chronic liver failure (ACLF) grade < 3, and SpO2 below 90% to improve survival of a patient with terlipressin treatment.
Claim 13 of the ‘572 application did not teach a dosage of terlipressin and pharmacokinetic or pharmacodynamic parameters.
The relevancy of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response as applied to claims 28-36 and 39-47 is described above not repeated here.
Because Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® teach an effective dosage of administered terlipressin and pharmacokinetic or pharmacodynamic parameters in patients associated with the administered dosage of terlipressin, one of ordinary skill in the art would have found it obvious to beneficially combine claim 13 of the ‘572 application with Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
Thus, claim 13 of the ‘572 application in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® are obvious to the instant claims 28-36 and 39-47.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
Claims 28-36 and 39-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 22 of copending Application No. 18/783,572 (the ‘572 application of 12/22/2025) in view of Jamil et al. (US 2016/0113994 A1, cited 9/24/2025) in view of (A) Boyer et al. (Journal of Hepatology. 2011; 55: 315-321, cited , cited 9/24/2025) for teaching SCr level, (B) Rodriguez et al. (J Hepatol. 2014 May;60(5):955-61, cited , cited 9/24/2025) for teaching ACLF grade, (C) Ling et al. (Sci Rep. 2017; 7: 42253) in view of Alexandria et al. (Hepatology. 2005;41:1282-1289) for teaching MELD score, (D) Lucassin (Ikaria, Inc. 2012, previously , cited 7/11/2025) in view of Wisniewski et al. (US 2016/0122386 A1, cited 7/11/2025), Alwadhi et al. (Indian Pediatr. 2017; 54: 729–734, cited 9/24/2025), and Bota et al. (The Journal of Emergency Medicine, Vol 13, No 3, pp 305- JIJ , 1995, cited 9/24/2025) for teaching SpO2 level, and (E) NCT02770716 (ver 13: 2018-08-09, cited 9/24/2025) and evidenced by Terlivaz® (Terlipressin product. revised:04/2023, cited 9/24/2025) for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response .
Claim 22 of the ‘572 application disclosed a method of administering terlipressin to a selected patient group with a baseline model end stage liver disease (MELD) score < 35, a serum creatinine (SCr) level< 5 mg/dl, and an acute-on-chronic liver failure (ACLF) grade < 3 to improve survival of a patient with terlipressin treatment.
Claim 22 of the ‘572 application did not disclose the selected patient with oxygen saturation (SpO2) ≥ 90%.
The relevancy of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response as applied to claims 28-36 and 39-47 is described above not repeated here.
Because Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® teach a patient’s baseline MELD score < 35, oxygen saturation of SpO2 ≥ 90%, ACLF grade < 3, and (SCr) level< 5 mg/dl likely response to terlipressin treatment, one of ordinary skill in the art would have found it obvious to beneficially combine claim 22 of the ‘572 application with Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
Claims 28-36 and 39-47 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 of 6/20/2025) in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
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Claim 1 of the ‘769 application disclosed a formulation of terlipressin acetate as follows.
Claim 1 of the ‘769 application did not disclose administration of terlipressin to treat hepatorenal syndrome of a selected patient group.
The relevancy of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response as applied to claims 28-36 and 39-47 is described above not repeated here.
Because Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® teach a patient’s baseline MELD score < 35, oxygen saturation of SpO2 ≥ 90%, ACLF grade < 3, and (SCr) level< 5 mg/dl likely response 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 (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
Thus, claim 1 of the ‘769 application in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® are obvious to the instant claims 28-36 and 39-47.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
Claims 28-36 and 39-47 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 of 6/20/2025) in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
Claim 1 of the ‘777 application disclosed a formulation of terlipressin acetate as follows:
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Claim 1 of the ‘777 application did not disclose administration of terlipressin to treat hepatorenal syndrome of a selected patient group.
The relevancy of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® for teaching terlipressin acetate formulation taught by Lucassin and inherent properties of terlipressin comprising patient’s response as applied to claims 28-36 and 39-47 is described above not repeated here.
Because Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® teach a patient’s baseline MELD score < 35, oxygen saturation of SpO2 ≥ 90%, ACLF grade < 3, and (SCr) level< 5 mg/dl likely response 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 (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz®.
Thus, claim 1 of the ‘777 application in view of Jamil et al. in view of (A) Boyer et al. for teaching SCr level, (B) Rodriguez et al. for teaching ACLF grade, (C) Ling et al. in view of Alexandria et al. for teaching MELD score, (D) Lucassin in view of Wisniewski et al., Alwadhi et al., and Bota et al. for teaching SpO2 level, and (E) NCT02770716 and evidenced by Terlivaz® are obvious to the instant claims 28-36 and 39-47.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 3/24/2026 have been fully considered but they are not persuasive because the arguments do not apply to the new ground of rejection with new references.
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
30-May-2026
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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