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 .
DETAILED ACTION
Status of Claims
Claims 1-11, 14-15, and 22-28 are pending and are under examination in the instant office action.
Information Disclosure Statement
Signed and initialed copies of the IDS papers filed on 5/18/2026, 1/20/2026, 1/15/2025 are enclosed in this action. The NPL document (001) listed in the IDS filed on 1/20/2026 is lined through because Applicants did not provide its English translation.
Each information disclosure statement must further include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information listed that is not in the English language. The concise explanation may be either separate from the specification or part of the specification. If the concise explanation is part of the specification, the IDS listing should include the page(s) or line(s) numbers where the concise explanation is located in the specification.
The requirement for a concise explanation of relevance is limited to information that is not in the English language. The explanation required is limited to the relevance as understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information at the time the information is submitted to the Office. If a complete translation of the information into English is submitted with the non-English language information, no concise explanation is required. An English-language equivalent application may be submitted to fulfill this requirement if it is, in fact, a translation of a foreign language application being listed in an information disclosure statement. There is no requirement for the translation to be verified. Submission of an English language abstract of a reference may fulfill the requirement for a concise explanation. Where the information listed is not in the English language, but was cited in a search report or other action by a foreign patent office in a counterpart foreign application, the requirement for a concise explanation of relevance can be satisfied by submitting an English-language version of the search report or action which indicates the degree of relevance found by the foreign office. This may be an explanation of which portion of the reference is particularly relevant, to which claims it applies, or merely an “X”, “Y”, or “A” indication on a search report. The requirement for a concise explanation of non-English language information would not be satisfied by a statement that a reference was cited in the prosecution of a United States application which is not relied on under 35 U.S.C. 120.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-11, 14-15, and 22-26 are rejected under 35 U.S.C. 103 as being unpatentable over Lagast et al. (Poster 21-A-127 presented at the North American Neuroendocrine Tumor Society NET Medical Symposium November 4 -6, 2021) and Madan et al. (Endocrine Abstract, 70 AEP627, 2020) in view of Delcò et al. (Drug Safety 2005; 28 (6): 529-545) as evidenced by US 20150157575. All references are cited in the IDS filed on 1/15/2025.
Lagast et al. disclose paltusotine (CRN00808) having the following structure:
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(3-[4-(4-amino-piperidin-1-yl)-3-(3,5-difluoro-phenyl)-quinolin-6-yl]-2-hydroxy-benzonitrile) as a first-in-class, oral, non-peptide somatostatin receptor type 2 (SST2) agonist (Title, Background, and Figure).
Lagast et al. disclose orally administering paltusotine once daily for the treatment of patients with acromegaly and carcinoid syndrome (CS) (Title, Background, and Conclusion).
Lagast et al. disclose paltusotine in capsule or tablet formulation (oral dosage form).
Lagast et al. disclose the 40 –60 mg/day dose of paltusotine achieves IGF-1 control comparable to depot SRLs in patients with acromegaly (Conclusion). Lagast et al. also disclose the 40 and 80 mg dose of the tablet formulation in the treatment of CS with the potential for up titration to a higher dose (Conclusion).
Madan et al. teaches the efficacy and safety of oral paltusotine (CRN00808) in patients with acromegaly (abstract). Madan et al. discloses that treatment emergent adverse events associated with paltusotine were generally mild and transient, and consistent with those reported with other somatostatin agonists and concludes that paltusotine has excellent drug-like properties for chronic once-daily oral treatment of patients with acromegaly and NETs (abstract). Also, Madan et al. discloses that the mean bioavailability of paltusotine was 70% and majority of the circulating drug-derived radioactivity is accounted for by unchanged paltusotine and there are no abundant circulating metabolites (abstract). In addition, Madan et al. further discloses that the primary route of excretion was the feces (89.9%) with minimal excretion in the urine (3.9% of dose) (abstract).
Lagast et al. and Madan et al. do not specifically teach that the patient has mild, moderate, or severe hepatic impairment. They also do not specifically teach determining that the patient has hepatic impairment, Child-Pugh score, and administering to those with hepatic impairment the same amount that would be administered to a patient who does not have hepatic impairment.
Delcò et al. teaches that for drugs that are new on the market, kinetic studies in patients with impaired hepatic function due to liver cirrhosis are requested by the drug agencies prior to approval. Delcò et al. further teaches that dosing recommendations for most of these drugs can, therefore, be found in the physician’s desk reference or similar publications, but usually only for patients with Child-Pugh class A or B, but not C (p536, col 2, para 3). Delcò et al. teach that drugs having a bioavailability that is ≥70% are low extraction drugs which undergo only a low extraction during the first passage across the liver and the bioavailability of low extraction drugs is not grossly affected by liver cirrhosis (hepatic impairment) (p535, col 2, 1.3.2-p536, col 1, para 1). Accordingly, therapy can be started with a normal dose while their clearance may be reduced depending on their hepatic metabolism and binding to albumin (p535, col 2, 1.3.2-p536, col 1, para 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer paltusotine to those with hepatic impairment in the same amount that would be administered to a patient who does not have hepatic impairment because of the following reasons. First, the patient population of Lagast et al. encompasses those with acromegaly who may or may not have hepatic impairment. Also, based on the teachings of Madan, one of ordinary skill in the art would have recognized that paltusotine is a low extraction drug and may not undergo hepatic metabolism, thus its bioavailability is not grossly affected by hepatic impairment and a normal dose can be administered as taught by Lagast et al. Thus, one of ordinary skill in the art would have been motivated to administer paltusotine in a normal dose which is used for those without hepatic impairment on the reasonable expectation that the bioavailability of paltusotine would not be affected by hepatic impairment as evidenced by Madan. Also, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine whether the bioavailability of a new drug such as paltusotine is affected by hepatic impairment because for new drugs on the market, kinetic studies in patients with impaired hepatic function are requested by the drug agencies prior to approval. Once the bioavailability of such new drug was not found to be affected by varying degree of hepatic impairment based on kinetic studies in patients with impaired hepatic function, it would have been obvious to administer the same therapeutically effective amount to those with mild, moderate or severe hepatic impairment on the reasonable expectation that the patient with hepatic impairment has similar plasma exposure of paltusotine as in a patient with normal hepatic function.
As to the Child-Pugh Score as recited in claim 8-11, it was well known in the art that the Child-Pugh Score is used as the basis for classification of clinical severity of hepatic impairment: 5 to 6 points - mild hepatic impairment, 7 to 9 points - moderate, 10 to 15 points - severe as evidenced by US 20150157575 ([0127]). Thus, it would have been obvious to determine clinical severity of hepatic impairment by using known parameter such as Child-Pugh Score.
Claims 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Lagast et al. (Poster 21-A-127 presented at the North American Neuroendocrine Tumor Society NET Medical Symposium November 4 -6, 2021) in view of Delcò et al. (Drug Safety 2005; 28 (6): 529-545) and Madan et al. (Endocrine Abstract, 70 AEP627, 2020) in further view of US 2019/0218202 (hereafter, Reddy, cited in IDS filed on 1/15/2025).
Lagast et al., Delcò et al. and Madan et al. as applied supra are herein applied for the same teachings in their entirety.
Lagast et al. do not specifically teach a hydrochloride salt of paltusotine, which is amorphous recited in claims 27-28.
Reddy discloses the use of paltusotine (3-[4-(4-amino-piperidin-1-yl)-3-(3,5-difluoro-phenyl)-quinolin-6-yl]-2-hydroxy-benzonitrile) in both free base and hydrochloride salt for the treatment of acromegaly and further discloses that the compound is amorphous ([0004], [0117], [0121], [0122], [0134], and [0135]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the amorphous hydrochloride salt of paltusotine in place of its free base form because Reddy teaches and suggest the use of paltusotine in an amorphous hydrochloride salt as well as free base for treating acromegaly. The skilled artisan would have been motivated to do so on the reasonable expectation that the amorphous salt form would have the same effects in the treatment of acromegaly as the free base form.
Non-Statutory Double Patenting Rejections
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
1. Claims 1-7, 14-15, and 22-28 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 6-9 of US patent 10597377.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of ‘377 patent are drawn to a method of treating acromegaly, a neuroendocrine tumor, or a combination thereof in a human comprising administering claimed compound (paltusotine) or its pharmaceutically acceptable salt to the human in need thereof. While the claims of the patent are silent about the patient having hepatic impairment, the patient population encompasses those with acromegaly and neuroendocrine tumor who may or may not have hepatic impairment. As such, the instant claims and those of the patent encompass overlapping subject matter and are obvious variant to each other. Also, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine whether the bioavailability of a new drug such as paltusotine is affected by hepatic impairment because for new drugs on the market, kinetic studies in patients with impaired hepatic function are requested by the drug agencies prior to approval. Once the bioavailability of such new drug was not found to be affected by varying degree of hepatic impairment based on kinetic studies in patients with impaired hepatic function, it would have been obvious to administer the same therapeutically effective amount to those with mild, moderate or severe hepatic impairment on the reasonable expectation that the patient with hepatic impairment has similar plasma exposure of paltusotine as in a patient with normal hepatic function.
As such, the instant claims would have been obvious over the claims of the patent.
2. Claims 1-7, 14-15, and 22-28 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-10 of US patent 10875839.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of ‘839 patent are drawn to a method of treating acromegaly in a human comprising orally administering claimed compound (paltusotine) or its pharmaceutically acceptable salt to the human in need thereof. While the claims of the patent are silent about the patient having hepatic impairment, the patient population encompasses those with acromegaly who may or may not have hepatic impairment. As such, the instant claims and those of the patent encompass overlapping subject matter and are obvious variant to each other. Also, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine whether the bioavailability of a new drug such as paltusotine is affected by hepatic impairment because for new drugs on the market, kinetic studies in patients with impaired hepatic function are requested by the drug agencies prior to approval. Once the bioavailability of such new drug was not found to be affected by varying degree of hepatic impairment based on kinetic studies in patients with impaired hepatic function, it would have been obvious to administer the same therapeutically effective amount to those with mild, moderate or severe hepatic impairment on the reasonable expectation that the patient with hepatic impairment has similar plasma exposure of paltusotine as in a patient with normal hepatic function.
As such, the instant claims would have been obvious over the claims of the patent.
3. Claims 1-7, 14-15, and 22-28 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-23 of US patent 11414397.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of ‘397 patent are drawn to a method of treating acromegaly, a neuroendocrine tumor, or a combination thereof in a human comprising administering claimed compound (2-2: 3-[4-(4-amino-piperidin-1-yl)-3-(3,5-difluoro-phenyl)-quinolin-6-yl]-2-hydroxy-benzonitrile) or its pharmaceutically acceptable salt to the human in need thereof. While the claims of the patent are silent about the patient having hepatic impairment, the patient population encompasses those with acromegaly and neuroendocrine tumor who may or may not have hepatic impairment. As such, the instant claims and those of the patent encompass overlapping subject matter and are obvious variant to each other. Also, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine whether the bioavailability of a new drug such as paltusotine is affected by hepatic impairment because for new drugs on the market, kinetic studies in patients with impaired hepatic function are requested by the drug agencies prior to approval. Once the bioavailability of such new drug was not found to be affected by varying degree of hepatic impairment based on kinetic studies in patients with impaired hepatic function, it would have been obvious to administer the same therapeutically effective amount to those with mild, moderate or severe hepatic impairment on the reasonable expectation that the patient with hepatic impairment has similar plasma exposure of paltusotine as in a patient with normal hepatic function.
4. Claims 1-7, 14-15, and 22-28 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-10 of US patent 10889561.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of ‘561 patent are drawn to a method of treating acromegaly, a neuroendocrine tumor, or a combination thereof in a human comprising administering a HCl salt of 3-[4-(4-amino-piperidin-1-yl)-3-(3,5-difluoro-phenyl)-quinolin-6-yl]-2-hydroxy-benzonitrile (paltusotine) to the human in need thereof. While the claims of the patent are silent about the patient having hepatic impairment, the patient population encompasses those with acromegaly and neuroendocrine tumor who may or may not have hepatic impairment. As such, the instant claims and those of the patent encompass overlapping subject matter and are obvious variant to each other. Also, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine whether the bioavailability of a new drug such as paltusotine is affected by hepatic impairment because for new drugs on the market, kinetic studies in patients with impaired hepatic function are requested by the drug agencies prior to approval. Once the bioavailability of such new drug was not found to be affected by varying degree of hepatic impairment based on kinetic studies in patients with impaired hepatic function, it would have been obvious to administer the same therapeutically effective amount to those with mild, moderate or severe hepatic impairment on the reasonable expectation that the patient with hepatic impairment has similar plasma exposure of paltusotine as in a patient with normal hepatic function.
As such, the instant claims would have been obvious over the claims of the patent.
5. Claims 1-7, 14-15, and 22-28 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 13, 25, and 26-27 of US patent 11266641.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of ‘641 patent are drawn to a method of treating acromegaly, a neuroendocrine tumor, or a combination thereof in a human comprising administering a tablet comprising 3-[4-(4-amino-piperidin-1-yl)-3-(3,5-difluoro-phenyl)-quinolin-6-yl]-2-hydroxy-benzonitrile (paltusotine) HCl to the human in need thereof. While the claims of the patent are silent about the patient having hepatic impairment, the patient population encompasses those with acromegaly and neuroendocrine tumor who may or may not have hepatic impairment. As such, the instant claims and those of the patent encompass overlapping subject matter and are obvious variant to each other. Also, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine whether the bioavailability of a new drug such as paltusotine is affected by hepatic impairment because for new drugs on the market, kinetic studies in patients with impaired hepatic function are requested by the drug agencies prior to approval. Once the bioavailability of such new drug was not found to be affected by varying degree of hepatic impairment based on kinetic studies in patients with impaired hepatic function, it would have been obvious to administer the same therapeutically effective amount to those with mild, moderate or severe hepatic impairment on the reasonable expectation that the patient with hepatic impairment has similar plasma exposure of paltusotine as in a patient with normal hepatic function.
As such, the instant claims would have been obvious over the claims of the patent.
6. Claims 1-7, 14-15, and 22-28 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-15 of US patent 11957674.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of ‘674 patent are drawn to a method of treating acromegaly or neuroendocrine tumor, or a combination thereof in a human comprising administering 3-[4-(4-amino-piperidin-1-yl)-3-(3,5-difluoro-phenyl)-quinolin-6-yl]-2-hydroxy-benzonitrile (paltusotine) or its pharmaceutically acceptable salt to the human in need thereof. While the claims of the patent are silent about the patient having hepatic impairment, the patient population encompasses those with acromegaly and neuroendocrine tumor who may or may not have hepatic impairment. As such, the instant claims and those of the patent encompass overlapping subject matter and are obvious variant to each other. Also, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine whether the bioavailability of a new drug such as paltusotine is affected by hepatic impairment because for new drugs on the market, kinetic studies in patients with impaired hepatic function are requested by the drug agencies prior to approval. Once the bioavailability of such new drug was not found to be affected by varying degree of hepatic impairment based on kinetic studies in patients with impaired hepatic function, it would have been obvious to administer the same therapeutically effective amount to those with mild, moderate or severe hepatic impairment on the reasonable expectation that the patient with hepatic impairment has similar plasma exposure of paltusotine as in a patient with normal hepatic function.
As such, the instant claims would have been obvious over the claims of the patent.
7. Claims 1-11, 14-15, and 22-28 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-27 of US patent 12208092.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of ‘674 patent are drawn to a method of treating acromegaly, carcinoid syndrome and/or neuroendocrine tumor in a human comprising administering 3-[4-(4-amino-piperidin-1-yl)-3-(3,5-difluoro-phenyl)-quinolin-6-yl]-2-hydroxy-benzonitrile (paltusotine) or its pharmaceutically acceptable salt to the human in need thereof, wherein the patient has hepatic impairment and the therapeutically effective amount of paltusotine, or a pharmaceutically acceptable salt thereof, is the same amount that would be administered to a patient who does not have hepatic impairment.
As such, the instant claims are anticipated by the claims of the patent.
Statutory Double Patenting Rejection
A rejection based on double patenting of the "same invention" type finds its support in the language of 35 U.S.C. 101 which states that "whoever invents or discovers any new and useful process ... may obtain a patent therefor ..." (Emphasis added). Thus, the term "same invention," in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957); and In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the conflicting claims so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 2 and 14-15 are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 11-13 of US patent 12208092.
Conclusion
No claims are allowed.
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/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611
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