DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/23/2026 has been entered.
Applicant’s amendment, filed 01/03/2026, has been entered.
Claims 1-31 have been canceled.
Claims 32-61 are pending and currently under examination as they read on a method treating a patient with type-1 hepatorenal syndrome (HRS-1) comprising administering terlipressin acetate.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 44-45, 49-50 are rejected under 35 U.S.C. 102(a)(1) are rejected as being anticipated by Wong et al. (NEJM March 2021; 384:818-828; including the Protocol and Supplemental Appendix made available with the full text of the Wong article at NEJM.org; reference of record).
Wong et al. taught a method for treating a patient having:
1) HRS-1, (see Wong et al. Abstract);
2) MELD score < 35, (see Wong et al. Table 1; Supplemental Appendix Figure S7);
3) Serum creatinine (Scr) level < 5 mg/dL (see Table 1 Wong et al.) and
4) ACLF grade < 3; (see Supplemental Appendix Table S8g);
Comprising the method steps of:
measuring the baseline serum creatinine level, (see Supplemental Appendix Fig S10);
intravenously administering a pharmaceutical composition comprising terlipressin (see Protocol page 6 of 90);
obtaining a Scr level during the initial 1-4 days of administration (Protocol Table 13-1; Supplemental Appendix Table S8);
continuing administration of the pharmaceutical composition until at least two Scr values less than or equal to 1.5 mg/dL (page 819, right column, second paragraph) and
obtaining a baseline oxygen saturation prior to administration (Protocol page 64 of 108; Vital signs).
Response to Applicant’s argument
Applicant argues that Wong does not teach HRS patients with MELD score, SCr level and ACLF grade as recited in the claims. In response, it is noted that the teachings of Wong have been clearly stated above. Therefore, Applicant’s argument has not been found convincing.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 32-43, 46-48, 51-61 are rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (NEJM March 2021; 384:818-828; including the Protocol and Supplementary Appendix made available with the full text of the Wong article at NEJM.org) in view of Jubran (Critical Care 2015; 19:272).
The teaching of Wong et al. has been discussed above (see 102).
In addition, Wong taught the following claim limitations (see below mapping)
claim
Prior art
32 e. f.
Protocol page 54 of 108
33
Protocol page 6 of 90 Initial Dosing
34-35
Protocol page 6 of 90 Dose Modifications
36
Protocol page 47 of 109
37
Protocol page 6 of 90 Treatment Discontinuation
38
Page 821 Table 1
39
Protocol page 5 of 90 Exclusion Criteria #3
52-54
Protocol pages 53-54 of 108
Moreover, given that the prior art taught the same method steps, it would necessarily yield patient with the above conditions having reduced adverse event up to 30 days, reduced mortality rate up to day 60 or improved 90-day survival compared to patients not meeting the conditions or the placebo group.
The only claim limitation Wong did not teach was that the HRS-1 patient having a baseline SpO2 greater than 90%. However, it would have been obvious for one of ordinary skill in the art to exclude patient with SpO2 baseline less than 90% or perform said monitoring throughout the course of treatment because Wong disclosed that terlipressin treatment was associated with respiratory failure (see, e.g., last paragraph on page 818). Upon reading the prior art teachings by, one of ordinary skill in the art would have been motivated to 1) take SpO2 reading before administering terlipressin; 2) not give terlipressin to patients whose SpO2 is less than 90% which is indicative of hypoxemia associated with respiratory failure and frequently in order to avoid hypoxia or respiratory symptoms. It is noted that oxygen saturation less than 90% is an art known marker for hypoxemia (see, e.g., Jubran on page 5, Clinical Applications). Therefore, one of ordinary skill in the art would have picked 90% as a threshold for detecting terlipressin-induced respiratory failure.
Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Applicant’s argument
Applicant further argues that Wong taught that patients in the terlipressin group were more likely to have adverse effect. In response, it is noted that Wong taught patients meeting the baseline criteria as recited in the present claims. Wong also stated that 176 of 200 patients in the terlipressin group reported adverse events. Therefore, the ones that did not experience adverse events would have been the patients meeting the baseline criteria.
Applicant’s arguments pertaining to unexpected results and long-felt need have been considered but have not been found convincing. The grounds of the 103 rejection herein are based on whether it would be obvious to select patients with an oxygen level > 90%. The subset population of the patients with the baseline criteria has been disclosed by Wong et al. These patients with the same criteria undergoing the same treatment as recited in the present claims would have the same outcome as recited in the claims, i.e., reduced incidence of adverse events or improved survival. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). Therefore, Applicant’s argument has not been found convincing.
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 32-61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 10,335,452 in view Wong et al. (NEJM March 2021; 384:818-828; including the Protocol and Supplementary Appendix made available with the full text of the Wong article at NEJM.org) in view of Jubran (Critical Care 2015; 19:272).
The claims of patent ‘452 disclosed a method of treating HRS comprising administering terlipressin and assessing Scr. Although the patent claims did not disclose obtaining SpO2, assessing an ACLF grade or monitoring SpO2 level, it would have been obvious to perform these steps in view of Wong et al. and Jubran et al. as evidenced by the instant specification as discussed above (see 102 and 103). Therefore, the patent claims render obvious of the present claims in view of Wong and Jubran.
Applicant’s argument and Examiner’s Response are essentially same as above.
Claims 32-61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the following in view of Wong et al. (NEJM March 2021; 384:818-828; including the Protocol and Supplemental Appendix made available with the full text of the Wong article at NEJM.org) in view of Jubran (Critical Care 2015; 19:272).
Co-pending application
Claims
USSN 17104864
claims 16, 18, 19, 27, 31-43
USSN 17340765
claims 1-48
USSN 17976502
Claims 1-27
USSN 17976603
Claims 1, 3, 5, 7-24
USSN 17976606
Claims 9-12, 16, 17, 19, 20, 24, 27, 28, 30-32
USSN 19213363
Claims 1-21
USSN 18783546
Claims 1-4
USSN 17587442
claims 1-19
USSN 18431587
Claims 17-46
USSN 18783572
Claims 13-42
The copending claims disclosed methods of treating comprising administering terlipressin in adults with HRS and obtaining SpO2, assessing an ACLF grade, monitoring SpO2 level and/or assessing SCr. Therefore, the reference copending claims would render obvious of the present claims in view of Wong et al., and Jubran et al. (see 102 and 103).
This is a provisional nonstatutory double patenting rejection.
Applicant’s argument and Examiner’s Response are essentially same as above.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHARON X WEN whose telephone number is (571)270-3064. The examiner can normally be reached Mon-Fri 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SHARON X WEN/Primary Examiner, Art Unit 1641
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