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 .
Priority
This application is a continuation of Application No. 16/140,365, filed 24 September 2018, which claims the benefit under 35 USC 119(e) of Application No. 62/563395, filed 26 September 2017. The effective filling date is 26 September 2017.
Claim Status
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on February 25, 2026. Claims 1-24 are canceled. Claims 25-36 and new claims 37-50 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/25/2026 has been considered by the examiner.
Action Summary
Claims 25-26, 28-30, 32-34, and 36-37 rejected under 35 U.S.C. 103 as being obvious over Badman (US2019/0076500 A1) in view of Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014), are maintained, but modified and revisited in light of the claim amendment.
Claims 25-37 rejected under 35 U.S.C. 103 as being obvious over Badman (US2019/0076500 A1) in view of Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014) as applied to claims 25-26, 28-30, 32-34, and 36-37 in further view of Boudes (US2015/0265560 A1), are also maintained, but modified and revised in light of the claim amendment.
Claims 25-37 rejected on the ground of non-statutory double patenting as being un-patentable over claims 1-6 of U.S. Patent No. 9,486,428; claims 1-9 of U.S Patent No. 9,.808,436 in view of Badman (US2019/0076500 A1), Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), Bergasa et al (CRC Press/Taylor & Francis; 2014), are maintained, but modified and revised in light of the claim amendment.
Claims 25-37 rejected on the ground of non-statutory double patenting as being un-patentable over claims 1-16 of U.S. Patent No. 10,272,058 in view of Badman (US2019/0076500 A1), Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014), are maintained, but modified and revised in light of the claim amendment.
Claims 25-36 rejected on the ground of non-statutory double patenting as being un-patentable over claims 1-16 of U.S. Patent No. 10,367,660 in view of Badman (US2019/0076500 A1), Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014), are maintained, but modified and revised in light of the claim amendment.
Claims 25-37 rejected on the ground of non-statutory double patenting as being un-patentable over claims 1-16 of U.S. Patent No. 11,596,614B2 in view of Badman (US2019/0076500 A1), Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014), are maintained, but modified and revised in light of the claim amendment.
Claims 25-37 rejected on the ground of non-statutory double patenting as being un-patentable over claims 1-16 of U.S. Patent No. 10,478,411 B2 in view of Badman (US2019/0076500 A1), Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014).
Claims 25-37 rejected on the ground of non-statutory double patenting as being un-patentable over claims 1-16 of U.S. Patent No. 10,272,058B2 in view of Badman (US2019/0076500 A1), Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014), are maintained, but modified and revised in light of the claim amendment.
New Rejection necessitated by claim amendment
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 25-50 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Independent claims 25 and 38 recited “in an amount equivalent to,” yet the specification as originally filed does not describe or provide any basis for determining such equivalence. Because this language introduces a concept not supported by the original specification, it constitutes new matter.
Modified and Revested Rejection
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 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.
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 non-obviousness.
Claims 25-26, 28-30, 32-34, and 36-39, 41-43, 45-47, and 49-50 are rejected under 35 U.S.C. 103 as being obvious over Badman (US2019/0076500 A1) in view of Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014)
Badman teaches a method a method for preventing, delaying or treating a liver disease or disorder including, but not limited to primary biliary cirrhosis, intrahepatic cholestasis, estrogen-induced cholestasis, drug-induced cholestasis, cholestasis of pregnancy, parenteral nutrition-associated cholestasis, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), in a patient in need therefor, comprising administering a therapeutically effective amount of
i) a FXR agonist, e.g., 2-[3-({5-cyclopropyl-3-[2-(trifluoromethoxy) phenyl]-1,2-oxazol-4-yl} methoxy)-8-azabicyclo [3.2.1] octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid and of
ii) seladelpar as an additional therapeutic agent, each of the components of the combination being administered simultaneously or sequentially and, in any order, or separate. (See claims 14 and 1-4.) Components (i) and (ii) can be administered together, one after the other or separately in one combined unit dose form or in two separate unit dose forms. (See paragraph [0048].) Another name for primary biliary cirrhosis is primary biliary cholangitis. The daily administration reads on once a day. Moreover, Badman teaches “combination” refers to either a fixed combination in one unit dosage form (e.g., capsule, tablet, or sachet), free (i.e. non-fixed) combination, or a kit of parts for the combined administration where a FXR agonist of the present invention and one or more “combination partner” (i.e. the additional therapeutic agent, such as e.g. seladelpar or a pharmaceutically acceptable salt or solvate thereof) may be administered independently at the same time or separately within time intervals, especially where these time intervals allow that the combination partners show a cooperative, e.g. synergistic effect. (See paragraph 0097.) The route of administration is oral. (See paragraph [0115].) Badman teaches during the treatment, there can be one or more periods of time, e.g. days, during which nor the FXR agonist of the invention or a caspase inhibitor, e.g. emricasan (in free form or as a pharmaceutically acceptable salt, solvate, prodrug and/or ester) neither the additional therapeutic agent, e.g. PPAR-delta agonist, e.g. elafibranor or seladelpar are administered to the patient (i.e. periods, e.g. days, void of combination treatment ) , or during which only one drug amongst the FXR agonist or the additional therapeutic agent is administered to the patient. (See paragraph [0135].) Badman also teaches seladelpar is to be administered at a dose in a range of about 2 mg, about 5 mg/day, about 10 mg/day, about 20 mg/day or about 50 mg, orally. (See paragraph [0167].) Additionally, Badman teaches the time interval between administration of the FXR agonist and of the additional therapeutic agent may vary from a few minutes to a few days, e.g., a few minutes, e.g., a few hours, e.g., 1 day to 1 week. (See paragraph [0136].) The fact that the time interval for the separate administration can be 1 day to 1 week of administration of the combination and in separate unit doss form, one can reasonably interpret the administration of saledalpar separately in its own unit dose form to meet the monotherapy to the subject. Badman teaches UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond. Since May 2016, another molecule has been approved in the US for the treatment of PBC, when combined with UDCA for primary biliary cholangitis (PBC) in adult patients with an inadequate response to UDCA, or as a single therapy in adults unable to tolerate UDCA. Lastly, Badman teaches the salt of seladelpar is Lysine (L-lysine) salt. (See paragraph [0028].)
Accordingly, the fact that Badman describes administering 2-[3-({5-cyclopropyl-3-[2-(trifluoromethoxy) phenyl]-1,2-oxazol-4-yl} methoxy)-8-azabicyclo [3.2.1] octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid and seladelpar separately-at a different time interval-it can indeed reasonably amount to a monotherapy at that specific time. Even though Badman defines the overall combination, it clearly shows that seladelpar is given at a certain time-without any other active ingredient at that moment-that can fall under a monotherapy scenario. Additionally, Badman explicitly discloses seladelpar in about 5 mg/day and about 10 mg/day. The claimed amount equivalent to 5 mg/day and the 10 mg/day does not confer a meaningful distinction, as no specialized equivalence is defined. Thus, a person of ordinary skill in the art would reasonably construe the amount taught by Badman be essentially be the same or obvious substitute for what’s claimed.
Badman does not teach cholestatic pruritus. Additionally, Badman does not the subject was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid.
Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, or hereditary pediatric cholestatic disorders and may accompany, although less frequently, many other liver diseases. (See Abstract.) Moreover, Beuers teaches
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Karon teaches the investigational peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis. (See first paragraph.) Moreover, Karon teaches primary biliary cholangitis, an important cause of end-stage liver disease, is initially associated with fatigue and pruritus and often responds inadequately to first-line treatment with ursodeoxycholic acid. MBX-8025 selectively activates the peroxisome proliferator–activated receptor delta, a nuclear receptor that regulates genes involved in lipid storage and transport. In prior studies, MBX-8025 decreased serum alkaline phosphatase (ALP) levels and seemed well tolerated in healthy volunteers and patients with dyslipidemia, the investigators noted. (See third paragraph.)
Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment. (See table 3 and the last paragraph of the left column of page 2052.).
Bergasa teaches cholestasis is defined as impaired secretion of bile. Pruritus is a complication of cholestasis including that associated with mutations in genes that code for transporters in the hepatocyte and from inflammatory liver diseases. (See first paragraph.)
Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. (Seven paragraph under Section 6.6.3.)
It would been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method of Badman that can include seladelpar as monotherapy by including a subject was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid to treat cholestatic pruritus to give Applicant’s claimed invention. One would have been motivated to so, because Badman teaches seladelpar as a PPAR-δ agonist that can treat various liver diseases including primary biliary cirrhosis and also teaching that UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond, and as a single therapy in adults unable to tolerate UDCA, because Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, because Karon teaches peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis, because Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment, and lastly because Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. One would reasonably expect the method of Badman to be effective for treating primary biliary cholangitis and its associated symptom cholestatic where the subject was previously on a stable and intolerant to ursodeoxycholic acid with success.
Claims 25-50 are rejected under 35 U.S.C. 103 as being obvious over Badman (US2019/0076500 A1) in view of Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014) as applied to claims 25-26, 28-30, 32-34, and 36-39, 41-43, 45-47, and 49-50 in further view of Boudes (US2015/0265560 A1),
The teachings of Badman, Beuers, Karon, Vrins, and Bergasa have been discussed supra.
Badman, Beuers, Karon, Vrins, and Bergasa collectively do not teach the l-lysine salt is
is L-lysine dihydrate as recited in claims 27, 31, 35, 40, 44 and 48.
Boudes teaches a method of treating an intrahepatic cholestatic disease by administering a therapeutically effective amount of MBX-8025 or a salt thereof, where the intrahepatic cholestatic disease is primary biliary cirrhosis. (See claims 1 and 21.) Primary biliary cirrhosis is the same as primary biliary cholangitis. Boudes also teaches common symptoms of cholestasis (e.g., primary biliary cirrhosis) includes pruritis and the Intrahepatic cholestatic diseases includes primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), progressive familial intrahepatic cholestasis (PFIC), and Alagille syndrome. (See paragraphs [0006] & [0007].) Moreover, Boudes teaches a method of treating an intrahepatic cholestatic disease by orally administering a therapeutically effective amount of MBX-8025 L-lysine dihydrate salt. (See claim 1.) The MBX-8025 L-lysine dihydrate salt is administered once/day. (See claim 27.) Boudes teaches MBX-8025 is currently formulated as its L-lysine dihydrate salt; MBX-8025 is another name for seladelpar. (See paragraph [0030].)
It would been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method of Badman by including the lysine dihydrate salt of seladelpar to give Applicant’s claimed invention. One would have been motivated to do so, because Beuers teaches Beuers teaches saladelpar (aka MBX-8025) currently formulated as dihydrate lysine salt can be used for treating primary biliary cirrhosis that includes pruritic. One would reasonably expect the inclusion of the L-lysine salt dihydrate to successfully enhance the efficacy and the properties of seladelpar for treating cholestatic pruritus.
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on February 25, 2026.
Applicant’s argument
Applicant argues that the disclosure of Badman when read as a whole, only shows some population did not respond to UDCA, and OCA, a bile-acid FXR agonist, was approved for treatment of PBC for patients intolerant or not responding to UDCA. It does not suggest anything about whether the use of seladelpar and/or non-bile acid FXR agonist of Badman would be effective in treating patient intolerant to UDCA
Examiner’s response
In response, the Examiner finds Applicant’s argument not persuasive. It may well be true that Badman does not suggest anything about whether the use of seladelpar and/or non-bile acid FXR agonist of would be effective in treating patient intolerant to UDCA. However, such suggestion is provided by Karon. Karon clearly shows that MBX-8025 was tested in patients who did not respond well to UDCA. Therefore, a person of ordinary skill in the art would reasonably expect MBX-8025 which is another for seladelpar (potentially linked to seladelpar-like effects) to be effective in treating patient intolerant to UDCA.
Applicant’s argument
Applicant argues that Badman, throughout the entire reference, is directed to a combination including the non-bile acid FXR agonist and an additional agent (e.g., seladelpar) and is not related to seladelpar monotherapy. However, the Office asserts that Badman discloses a potential time interval (such as 1 day to 1 week) between administration of the FXR agonist and the additional agent (e.g., seladelpar), and that such individual administration of seladelpar within the combination therapy can be interpreted as seladelpar monotherapy. 3 Applicant respectfully disagrees, and submits that such interpretation is far from the plain meaning of monotherapy and thus unreasonable. Applicant respectfully submits that the alternating administration of the combination of Badman cannot reasonably suggest the seladelpar monotherapy of claim 25 to a person skilled in the ordinary art.
Examiner’s response
In response, the Examiner finds Applicant’s argument not persuasive. Again, Badman teaches flexibility-it talks about combination therapies but also mentions intervals where seladelpar and the FXR agonist are administered separately at different time interval. From that teaching, a person of ordinary skill in the art could reasonably derive monotherapy use. Badman clearly suggest the use of seladelpar on its own at any point-even temporarily-that seems to indicate monotherapy is not an inventive leap.
Applicant’s argument
Applicant argues that in view of the above, Applicant respectfully submits that the Office did not fully recognize the difference between the claimed method and disclosure of Badman, and Badman does not teach or suggest the claimed method. Rather, as a whole, Badman, which is directed to treatment of liver disease with a combination of non-bile acid FXR agonist and additional therapeutic agent, is fundamentally different from the claimed method. Badman is not concerned about I) treating cholestatic pruritus, 2) treating a subject intolerant to UDCA, or 3) administering seladelpar as a monotherapy. Despite such failures, the Office contends that one would have been motivated to modify the method of Badman to arrive at the claimed methods. 4 Applicant respectfully disagrees. Badman is focused on treating liver disease and does not even recognize the problem or need for treating pruritus, and the Office failed to clearly establish such desirability to modify Badman's method to arrive at the claimed method for treating pruritus. It has been established that the mere fact that the cited art can be combinable or modifiable in a manner that will yield the claimed invention would not simply make such modification obvious, without additional suggestion of the desirability of such modification.
Examiner’s response
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the present case, the arguments improperly focus on Badman in isolation, whereas the rejection relies on the combined teachings of Badman in view of Beuers, Karon, and Bergasa. With respect to the treatment of pruritus, Beuers and Bergasa teach that pruritus is a well-known symptom associated with cholestatic liver diseases such as primary biliary cholangitis. Thus, a person of ordinary skill in the art would have reasonably expected that treating the underlying cholestatic condition as taught by Badman would also treat associated pruritus. Regarding the claimed patient population, Karon teaches administration of MBX-8025 (a PPAR agonist related to seladelpar) in patients who respond inadequately to ursodeoxycholic acid (UDCA), thereby explicitly suggesting treatment of the same patient subgroup recited in the claims. Applicant’s argument that Badman is limited to combination therapy is also unpersuasive. Badman expressly teaches that the therapeutic agents may be administered simultaneously or sequentially, in any order, and even separately with time intervals ranging from minutes to days. Additionally, Badman discloses treatment periods during which only one agent is administered. Such disclosures would have reasonably suggested to one of ordinary skill in the art that each agent, including seladelpar, is independently effective and could be administered alone. Therefore, the claimed “monotherapy” represents no more than an obvious variation of the prior art methods.
Applicant’s argument
Applicant argument with respect to claim 38 is the same arguments presented for claims 38.
Examiner’s response
In response, the Examiner finds Applicant’s argument not persuasive. The Examiner rationale on claim 25 logically extends to claim 38.
Applicant’s argument
Applicant argues Vrins is an article disclosing that PP AR delta activation leads to stimulation of transintestinal cholesterol efflux. However, this does not suggest whether seladelpar Bergasa is a chapter in a book regarding the mechanism of cholestatic pruritus. Bergasa discloses that "the pathogenesis of the pruritus of cholestasis is, most likely, multifactorial. ...” Bergasa discloses that "pruritogen(s) that mediates the pruritus is made in the liver and excreted in bile and that, as a result of cholestasis accumulates in body tissue and by some mechanism triggers the sensation of itch ... the nature of pruritogen, however, is unknown." (emphasis added). 17 In sum, the cited references do not teach or suggest that seladelpar would be effective in treating pruritus. Further, Badman discloses that OCA was approved for treatment of PBC but worsened pruritus, so the effectiveness in the treatment of PBC does not provide reasonable expectation of success in the treatment of cholestatic pruritus. Bergasa further supports this, by disclosing that the mechanism of cholestatic pruritus is unclear, and it would be difficult to predict whether seladelpar (or any other drug) would be effective in treating cholestatic pruritus. Applicant respectfully submits that there is no motivation to modify Badman or combine these multiple references and the cited references do not suggest the reasonable expectation of effectiveness of seladelpar in combination with UDCA in treating cholestatic pruritus in a subject previously on a stable and recommended dose of UDCA. Thus, no prima facie obviousness is established for claim 38 and the claims that depend therefrom.
Examiner’s response
In response, the Examiner finds Applicant’s argument not persuasive. Vrins shows PPAr-δ acdtiviation in cholesterol influx. While it does not mention seladelpar directly, Vrins support the role of pathways in condition of bile metabolism. Bergass explicitly connects pruritus as a complication of cholestasis, which is associated with transporter gene mutations. Badman not only show seladelpar can be administered separately within a certain timeframe with and FXR agonist and also demonstrates that OCA for the treatment of PBC, when combined with UDCA for primary biliary cholangitis (PBC) in adult patients with an inadequate response to UDCA, or as a single therapy in adults unable to tolerate UDCA. This provides a direct motivation to seek alternatives agents that can treat PBC and its related side effects such as pruritus. Karon teaches MXB-2085 (aka seladelpar) is antipruritic. Given these references, a skilled parson would have motivation to explore seladelpar, an antipruritic agent, as a solution to prutitus in cholestasis. Thus, a reasonable expectation of success exists, and the rejection stands.
Applicant’s argument
Applicant argues before the effective filing date of the present application, ursodeoxycholic acid (UDCA) and OCA were approved and standard therapies for the treatment of PBC. See Nevens et al. (2016) and the present specification [0026]-[0027]. However, it was well known that UDCA is not effective in treating pruritus. See, e.g., the specification [0026] and Trivedi et al (2017) (submitted in the IDS herewith). Also, as discussed above, OCA worsened pruritus while being administered to PBC patients. Accordingly, while these drugs might be effective for PBC, they were not suitable for treating PBC-associated cholestatic pruritus.
On the other hand, as shown in Examples 1-2 of the present application, seladelpar is effective for treating both PBC and also PBC-associated cholestatic pruritus. In fact, seladelpar was
approved for the treatment of PBC in 2024 as LIVDELZI®. The product label for LIVDELZI®
discloses that "[p]atients treated with LIVDELZI® demonstrated greater improvement in pruritus
compared with placebo." Accordingly, contrary to previously known therapies for PBC (i.e., UDCA and OCA), seladelpar shows superior property of effectiveness for treating both PBC and PBC-associated cholestatic pruritus, making it suitable for treatment of cholestatic pruritus. Such superior effect is not suggested by any of the cited references.
Examiner’s response
In response, the Examiner finds Applicant’s argument not persuasive. Applicant’s argument relies on the assertion that UDCA and OCA worsened or failed to treat pruritus. However, the question is not whether UDCA or OCA were ideal; it is whether the prior art teaches or suggest a reasonable expectation of success using seladelpar. The prior art suggests investigating alternative treatments for pruritus in PBC contexts. The fact seladepar ultimately showed clinical success later does not negate whether it would have been obvious to use it at the time of filing for treating cholestatic pruritus. Moreover, the applicant’s reliance on the 2024 Livdelzi product label is post-filing data. While those results may show clinical superiority later, obviousness rejection is judged at the time of filing. The question is whether a person of ordinary skill in the art would have had a reason to use seladepar which is known to be an antipruritic agent based on the prior art. The cited references, including known challenges with UDCA and OCA, would have a motivation to investigate alternative agents. Whether or not the superior results were later demonstrated does not rebut the initial obviousness determination, since the prior art already provided the motivation to pursue seladelpar as a cholestatic pruritus’ treatment. Therefore, the rejection remains proper.
Double Patenting
The non-statutory 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 time-wise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A non-statutory 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 non-statutory 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 §§ 706.02(l)(1) - 706.02(l)(3) 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.
Claims 25-50 are rejected on the ground of non-statutory double patenting as being un-patentable over claims 1-6 of U.S. Patent No. 9,486,428; claims 1-9 of U.S Patent No. 9,.808,436 in view of Badman (US2019/0076500 A1), Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), Bergasa et al (CRC Press/Taylor & Francis; 2014),
The U.S. patent claims teach a method of treating primary biliary cholangitis and primary sclerosing cholangitis by orally administering a therapeutically effective amount of MBX-8025 L-lysine dihydrate salt, see claims 1-3. The MBX-8025 L-lysine dihydrate salt is administered once/day. The U.S. patent claims teach the daily dose of MBX-8025 L-lysine dihydrate salt (when calculated as the free acid) is 20-200 mg/day. While the prior art does not specifically teach amount equivalent to 5 mg/day or 10 mg/day claimed, the prior art teaching of 20-200 mg/day touches the 5 mg/day or 10 mg/day claimed. The prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
The U.S. patent claims do not teach primary biliary cholangitis-associated cholestatic pruritus in a subject that was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid. The U.S. patent claims do not teach an amount equivalent to 5 mg/day or 10 mg/day.
Badman teaches a method a method for preventing, delaying or treating a liver disease or disorder including, but not limited to primary biliary cirrhosis, in a patient in need therefor, comprising administering a therapeutically effective amount of
i) a FXR agonist, e.g., 2-[3-({5-cyclopropyl-3-[2-(trifluoromethoxy) phenyl]-1,2-oxazol-4-yl} methoxy)-8-azabicyclo [3.2.1] octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid and of
ii) seladelpar as an additional therapeutic agent, each of the components of the combination being administered simultaneously or sequentially and, in any order, or separate. (See claims 14 and 1-4.) Components (i) and (ii) can be administered together, one after the other or separately in one combined unit dose form or in two separate unit dose forms. (See paragraph [0048].) Another name for primary biliary cirrhosis is primary biliary cholangitis. The daily administration reads on once a day. Moreover, Badman teaches “combination” refers to either a fixed combination in one unit dosage form (e.g., capsule, tablet, or sachet), free (i.e. non-fixed) combination, or a kit of parts for the combined administration where a FXR agonist of the present invention and one or more “combination partner” (i.e. the additional therapeutic agent, such as e.g. seladelpar or a pharmaceutically acceptable salt or solvate thereof) may be administered independently at the same time or separately within time intervals, especially where these time intervals allow that the combination partners show a cooperative, e.g. synergistic effect. (See paragraph 0097.) The route of administration is oral. (See paragraph [0115].) Badman also teaches seladelpar is to be administered at a dose in a range of about 2 mg, about 5 mg/day, about 10 mg/day, about 20 mg/day or about 50 mg, orally. (See paragraph [0167].) Additionally, Badman teaches the time interval between administration of the FXR agonist and of the additional therapeutic agent may vary from a few minutes to a few days, e.g., a few minutes, e.g., a few hours, e.g., 1 day to 1 week. (See paragraph [0136].) The fact that the time interval for the separate administration can be 1 day to 1 week of administration of the combination and in separate unit doss form, one can reasonably interpret the administration of saledalpar separately in its own unit dose form to meet the consisting of language. Badman teaches UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond. Since May 2016, another molecule has been approved in the US for the treatment of PBC, when combined with UDCA for primary biliary cholangitis (PBC) in adult patients with an inadequate response to UDCA, or as a single therapy in adults unable to tolerate UDCA. Lastly, Badman teaches the salt of seladelpar is Lysine (L-lysine) salt. (See paragraph [0028].) The claimed amount equivalent to 5 mg/day and the 10 mg/day does not confer a meaningful distinction, as no specialized equivalence is defined. Thus, a person of ordinary skill in the art would reasonably construe the amount taught by Badman be essentially be the same or obvious substitute for what’s claimed.
Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, or hereditary pediatric cholestatic disorders and may accompany, although less frequently, many other liver diseases. (See Abstract.) Moreover, Beuers teaches
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Karon teaches the investigational peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis. (See first paragraph.) Moreover, Karon teaches primary biliary cholangitis, an important cause of end-stage liver disease, is initially associated with fatigue and pruritus and often responds inadequately to first-line treatment with ursodeoxycholic acid. MBX-8025 selectively activates the peroxisome proliferator–activated receptor delta, a nuclear receptor that regulates genes involved in lipid storage and transport. In prior studies, MBX-8025 decreased serum alkaline phosphatase (ALP) levels and seemed well tolerated in healthy volunteers and patients with dyslipidemia, the investigators noted. (See third paragraph.)
Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment. (See table 3 and the last paragraph of the left column of page 2052.).
Bergasa teaches cholestasis is defined as impaired secretion of bile. Pruritus is a complication of cholestasis including that associated with mutations in genes that code for transporters in the hepatocyte and from inflammatory liver diseases. (See first paragraph.)
Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. (Seven paragraph under Section 6.6.3.)
It would been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method of the U.S. patent claims that can include seladelpar lysine dihydrate salt in the amount equivalent to of 5 mg/day or 10 mg/day as monotherapy by including a subject was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid to treat cholestatic pruritus to give Applicant’s claimed invention. One would have been motivated to so, because Badman teaches seladelpar as a PPAR-δ agonist that can treat various liver diseases including primary biliary cirrhosis and also teaching that UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond, and as a single therapy in adults unable to tolerate UDCA, because Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, because Karon teaches peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis, because Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment, and lastly because Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. One would reasonably expect the method of the U.S. patent claims to be effective for treating primary biliary cholangitis and its associated symptom cholestatic where the subject was previously on a stable and intolerant to ursodeoxycholic acid with success.
Claims 25-50 are rejected on the ground of non-statutory double patenting as being un-patentable over claims 1-16 of U.S. Patent No. 10,272,058 in view of Badman (US2019/0076500 A1), Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014).
The U.S. patent claims teach a method of treating primary biliary cholangitis by administering seladelpar or a salt thereof, where the daily dose of seladelpar or a salt thereof is 5 mg and 10 mg, when the dose is calculated as seladelpar, see claims 1 and 9. The seladelpar or a salt thereof is seladelpar L-lysine dihydrate salt, see claim 2. The seladelpar or a salt thereof is administered orally once/day, see claims 4-6.
The U.S. patent claims do not teach primary biliary cholangitis-associated cholestatic pruritus in a subject that was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid.
Badman teaches a method a method for preventing, delaying or treating a liver disease or disorder including, but not limited to primary biliary cirrhosis, in a patient in need therefor, comprising administering a therapeutically effective amount of
i) a FXR agonist, e.g., 2-[3-({5-cyclopropyl-3-[2-(trifluoromethoxy) phenyl]-1,2-oxazol-4-yl} methoxy)-8-azabicyclo [3.2.1] octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid and of
ii) seladelpar as an additional therapeutic agent, each of the components of the combination being administered simultaneously or sequentially and, in any order, or separate. (See claims 14 and 1-4.) Components (i) and (ii) can be administered together, one after the other or separately in one combined unit dose form or in two separate unit dose forms. (See paragraph [0048].) Another name for primary biliary cirrhosis is primary biliary cholangitis. The daily administration reads on once a day. Moreover, Badman teaches “combination” refers to either a fixed combination in one unit dosage form (e.g., capsule, tablet, or sachet), free (i.e. non-fixed) combination, or a kit of parts for the combined administration where a FXR agonist of the present invention and one or more “combination partner” (i.e. the additional therapeutic agent, such as e.g. seladelpar or a pharmaceutically acceptable salt or solvate thereof) may be administered independently at the same time or separately within time intervals, especially where these time intervals allow that the combination partners show a cooperative, e.g. synergistic effect. (See paragraph 0097.) The route of administration is oral. (See paragraph [0115].) Badman also teaches seladelpar is to be administered at a dose in a range of about 2 mg, about 5 mg/day, about 10 mg/day, about 20 mg/day or about 50 mg, orally. (See paragraph [0167].) Additionally, Badman teaches the time interval between administration of the FXR agonist and of the additional therapeutic agent may vary from a few minutes to a few days, e.g., a few minutes, e.g., a few hours, e.g., 1 day to 1 week. (See paragraph [0136].) The fact that the time interval for the separate administration can be 1 day to 1 week of administration of the combination and in separate unit doss form, one can reasonably interpret the administration of saledalpar separately in its own unit dose form to meet the consisting of language. Badman teaches UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond. Since May 2016, another molecule has been approved in the US for the treatment of PBC, when combined with UDCA for primary biliary cholangitis (PBC) in adult patients with an inadequate response to UDCA, or as a single therapy in adults unable to tolerate UDCA. Lastly, Badman teaches the salt of seladelpar is Lysine (L-lysine) salt. (See paragraph [0028].) The claimed amount equivalent to 5 mg/day and the 10 mg/day does not confer a meaningful distinction, as no specialized equivalence is defined. Thus, a person of ordinary skill in the art would reasonably construe the amount taught by Badman be essentially be the same or obvious substitute for what’s claimed.
Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, or hereditary pediatric cholestatic disorders and may accompany, although less frequently, many other liver diseases. (See Abstract.) Moreover, Beuers teaches
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Karon teaches the investigational peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis. (See first paragraph.) Moreover, Karon teaches primary biliary cholangitis, an important cause of end-stage liver disease, is initially associated with fatigue and pruritus and often responds inadequately to first-line treatment with ursodeoxycholic acid. MBX-8025 selectively activates the peroxisome proliferator–activated receptor delta, a nuclear receptor that regulates genes involved in lipid storage and transport. In prior studies, MBX-8025 decreased serum alkaline phosphatase (ALP) levels and seemed well tolerated in healthy volunteers and patients with dyslipidemia, the investigators noted. (See third paragraph.)
Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment. (See table 3 and the last paragraph of the left column of page 2052.).
Bergasa teaches cholestasis is defined as impaired secretion of bile. Pruritus is a complication of cholestasis including that associated with mutations in genes that code for transporters in the hepatocyte and from inflammatory liver diseases. (See first paragraph.)
Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. (Seven paragraph under Section 6.6.3.)
It would been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method of the U.S. patent claims that can include seladelpar lysine dihydrate salt in an amount equivalent to 5 mg/day or 10 mg/day as monotherapy by including a subject was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid to treat cholestatic pruritus to give Applicant’s claimed invention. One would have been motivated to so, because Badman teaches seladelpar as a PPAR-δ agonist that can treat various liver diseases including primary biliary cirrhosis and also teaching that UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond, and as a single therapy in adults unable to tolerate UDCA, because Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, because Karon teaches peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis, because Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment, and lastly because Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. One would reasonably expect the method of the U.S. patent claims to be effective for treating primary biliary cholangitis and its associated symptom cholestatic where the subject was previously on a stable and intolerant to ursodeoxycholic acid with success.
Claims 25-50 are rejected on the ground of non-statutory double patenting as being un-patentable over claims 1-16 of U.S. Patent No. 10,367,660 in view of Badman (US2019/0076500 A1), Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014).
The U.S. patent claims teach a method of treating primary sclerosing cholangitis by administering seladelpar or a salt thereof, where the daily dose of seladelpar or a salt thereof is 5 mg and 10 mg, when the dose is calculated as seladelpar, see claims 1 and 9. The seladelpar or a salt thereof is seladelpar L-lysine dihydrate salt, see claim 2. The seladelpar or a salt thereof is administered orally once/day, see claims 1-16. The claimed amount equivalent to 5 mg/day and the 10 mg/day does not confer a meaningful distinction, as no specialized equivalence is defined. Thus, a person of ordinary skill in the art would reasonably construe the amount taught by the U.S. patent be essentially be the same or obvious substitute for what’s claimed.
The U.S. patent claims do not teach primary biliary cholangitis-associated cholestatic pruritus in a subject suffering from primary biliary cholangitis during treatment of the primary biliary cholangitis, the subject being on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid.
The U.S. patent claims do not teach primary biliary cholangitis-associated cholestatic pruritus in a subject that was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid.
Badman teaches a method a method for preventing, delaying or treating a liver disease or disorder including, but not limited to primary biliary cirrhosis, in a patient in need therefor, comprising administering a therapeutically effective amount of
i) a FXR agonist, e.g., 2-[3-({5-cyclopropyl-3-[2-(trifluoromethoxy) phenyl]-1,2-oxazol-4-yl} methoxy)-8-azabicyclo [3.2.1] octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid and of
ii) seladelpar as an additional therapeutic agent, each of the components of the combination being administered simultaneously or sequentially and, in any order, or separate. (See claims 14 and 1-4.) Components (i) and (ii) can be administered together, one after the other or separately in one combined unit dose form or in two separate unit dose forms. (See paragraph [0048].) Another name for primary biliary cirrhosis is primary biliary cholangitis. The daily administration reads on once a day. Moreover, Badman teaches “combination” refers to either a fixed combination in one unit dosage form (e.g., capsule, tablet, or sachet), free (i.e. non-fixed) combination, or a kit of parts for the combined administration where a FXR agonist of the present invention and one or more “combination partner” (i.e. the additional therapeutic agent, such as e.g. seladelpar or a pharmaceutically acceptable salt or solvate thereof) may be administered independently at the same time or separately within time intervals, especially where these time intervals allow that the combination partners show a cooperative, e.g. synergistic effect. (See paragraph 0097.) The route of administration is oral. (See paragraph [0115].) Badman also teaches seladelpar is to be administered at a dose in a range of about 2 mg, about 5 mg/day, about 10 mg/day, about 20 mg/day or about 50 mg, orally. (See paragraph [0167].) Additionally, Badman teaches the time interval between administration of the FXR agonist and of the additional therapeutic agent may vary from a few minutes to a few days, e.g., a few minutes, e.g., a few hours, e.g., 1 day to 1 week. (See paragraph [0136].) The fact that the time interval for the separate administration can be 1 day to 1 week of administration of the combination and in separate unit doss form, one can reasonably interpret the administration of saledalpar separately in its own unit dose form to meet the consisting of language. Badman teaches UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond. Since May 2016, another molecule has been approved in the US for the treatment of PBC, when combined with UDCA for primary biliary cholangitis (PBC) in adult patients with an inadequate response to UDCA, or as a single therapy in adults unable to tolerate UDCA. Lastly, Badman teaches the salt of seladelpar is Lysine (L-lysine) salt. (See paragraph [0028].)
Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, or hereditary pediatric cholestatic disorders and may accompany, although less frequently, many other liver diseases. (See Abstract.) Moreover, Beuers teaches
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Karon teaches the investigational peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis. (See first paragraph.) Moreover, Karon teaches primary biliary cholangitis, an important cause of end-stage liver disease, is initially associated with fatigue and pruritus and often responds inadequately to first-line treatment with ursodeoxycholic acid. MBX-8025 selectively activates the peroxisome proliferator–activated receptor delta, a nuclear receptor that regulates genes involved in lipid storage and transport. In prior studies, MBX-8025 decreased serum alkaline phosphatase (ALP) levels and seemed well tolerated in healthy volunteers and patients with dyslipidemia, the investigators noted. (See third paragraph.)
Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment. (See table 3 and the last paragraph of the left column of page 2052.).
Bergasa teaches cholestasis is defined as impaired secretion of bile. Pruritus is a complication of cholestasis including that associated with mutations in genes that code for transporters in the hepatocyte and from inflammatory liver diseases. (See first paragraph.)
Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. (Seven paragraph under Section 6.6.3.)
It would been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method of the U.S. patent claims that can include seladelpar lysine dihydrate salt as monotherapy by including a subject was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid to treat cholestatic pruritus to give Applicant’s claimed invention. One would have been motivated to so, because Badman teaches seladelpar as a PPAR-δ agonist that can treat various liver diseases including primary biliary cirrhosis and also teaching that UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond, and as a single therapy in adults unable to tolerate UDCA, because Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, because Karon teaches peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis, because Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment, and lastly because Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. One would reasonably expect the method of the U.S. patent claims to be effective for treating primary biliary cholangitis and its associated symptom cholestatic where the subject was previously on a stable and intolerant to ursodeoxycholic acid with success.
Claims 25-50 are rejected on the ground of non-statutory double patenting as being un-patentable over claims 1-16 of U.S. Patent No. 11,596,614B2 in view of Badman (US2019/0076500 A1), Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014).
The U.S. patent claims teach a method of treating intrahepatic cholestatic disease by administering seladelpar or a salt thereof, where the daily dose of seladelpar or a salt thereof is 5 mg and 10 mg, when the dose is calculated as seladelpar, see claims 1 and 9. The seladelpar or a salt thereof is seladelpar L-lysine dihydrate salt, see claim 2. The seladelpar or a salt thereof is administered orally once/day, see claims 1-16. The claimed amount equivalent to 5 mg/day and the 10 mg/day does not confer a meaningful distinction, as no specialized equivalence is defined. Thus, a person of ordinary skill in the art would reasonably construe the amount taught by Badman be essentially be the same or obvious substitute for what’s claimed.
The U.S. patent claims do not teach primary biliary cholangitis-associated cholestatic pruritus in a subject suffering from primary biliary cholangitis during treatment of the primary biliary cholangitis where the subject was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid.
Badman teaches a method a method for preventing, delaying or treating a liver disease or disorder including, but not limited to primary biliary cirrhosis, in a patient in need therefor, comprising administering a therapeutically effective amount of
i) a FXR agonist, e.g., 2-[3-({5-cyclopropyl-3-[2-(trifluoromethoxy) phenyl]-1,2-oxazol-4-yl} methoxy)-8-azabicyclo [3.2.1] octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid and of
ii) seladelpar as an additional therapeutic agent, each of the components of the combination being administered simultaneously or sequentially and, in any order, or separate. (See claims 14 and 1-4.) Components (i) and (ii) can be administered together, one after the other or separately in one combined unit dose form or in two separate unit dose forms. (See paragraph [0048].) Another name for primary biliary cirrhosis is primary biliary cholangitis. The daily administration reads on once a day. Moreover, Badman teaches “combination” refers to either a fixed combination in one unit dosage form (e.g., capsule, tablet, or sachet), free (i.e. non-fixed) combination, or a kit of parts for the combined administration where a FXR agonist of the present invention and one or more “combination partner” (i.e. the additional therapeutic agent, such as e.g. seladelpar or a pharmaceutically acceptable salt or solvate thereof) may be administered independently at the same time or separately within time intervals, especially where these time intervals allow that the combination partners show a cooperative, e.g. synergistic effect. (See paragraph 0097.) The route of administration is oral. (See paragraph [0115].) Badman also teaches seladelpar is to be administered at a dose in a range of about 2 mg, about 5 mg/day, about 10 mg/day, about 20 mg/day or about 50 mg, orally. (See paragraph [0167].) Additionally, Badman teaches the time interval between administration of the FXR agonist and of the additional therapeutic agent may vary from a few minutes to a few days, e.g., a few minutes, e.g., a few hours, e.g., 1 day to 1 week. (See paragraph [0136].) The fact that the time interval for the separate administration can be 1 day to 1 week of administration of the combination and in separate unit doss form, one can reasonably interpret the administration of saledalpar separately in its own unit dose form to meet the consisting of language. Badman teaches UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond. Since May 2016, another molecule has been approved in the US for the treatment of PBC, when combined with UDCA for primary biliary cholangitis (PBC) in adult patients with an inadequate response to UDCA, or as a single therapy in adults unable to tolerate UDCA. Lastly, Badman teaches the salt of seladelpar is Lysine (L-lysine) salt. (See paragraph [0028].)
Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, or hereditary pediatric cholestatic disorders and may accompany, although less frequently, many other liver diseases. (See Abstract.) Moreover, Beuers teaches
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Karon teaches the investigational peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis. (See first paragraph.) Moreover, Karon teaches primary biliary cholangitis, an important cause of end-stage liver disease, is initially associated with fatigue and pruritus and often responds inadequately to first-line treatment with ursodeoxycholic acid. MBX-8025 selectively activates the peroxisome proliferator–activated receptor delta, a nuclear receptor that regulates genes involved in lipid storage and transport. In prior studies, MBX-8025 decreased serum alkaline phosphatase (ALP) levels and seemed well tolerated in healthy volunteers and patients with dyslipidemia, the investigators noted. (See third paragraph.)
Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment. (See table 3 and the last paragraph of the left column of page 2052.).
Bergasa teaches cholestasis is defined as impaired secretion of bile. Pruritus is a complication of cholestasis including that associated with mutations in genes that code for transporters in the hepatocyte and from inflammatory liver diseases. (See first paragraph.)
Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. (Seven paragraph under Section 6.6.3.)
It would been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method of the U.S. patent claims that can include seladelpar lysine dihydrate salt as monotherapy by including a subject was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid to treat cholestatic pruritus to give Applicant’s claimed invention. One would have been motivated to so, because Badman teaches seladelpar as a PPAR-δ agonist that can treat various liver diseases including primary biliary cirrhosis and also teaching that UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond, and as a single therapy in adults unable to tolerate UDCA, because Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, because Karon teaches peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis, because Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment, and lastly because Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. One would reasonably expect the method of the U.S. patent claims to be effective for treating primary biliary cholangitis and its associated symptom cholestatic where the subject was previously on a stable and intolerant to ursodeoxycholic acid with success.
Claims 25-50 are rejected on the ground of non-statutory double patenting as being un-patentable over claims 1-16 of U.S. Patent No. 10,478,411 B2 in view of Badman (US2019/0076500 A1), Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014).
The U.S. patent claims teach a method of treating primary sclerosing cholangitis by administering seladelpar or a salt thereof, where the daily dose of seladelpar or a salt thereof is 5 mg and 10 mg, when the dose is calculated as seladelpar, see claims 1 and 9. The seladelpar or a salt thereof is seladelpar L-lysine dihydrate salt, see claim 2. The seladelpar or a salt thereof is administered orally once/day, see claims 1-16. The claimed amount equivalent to 5 mg/day and the 10 mg/day does not confer a meaningful distinction, as no specialized equivalence is defined. Thus, a person of ordinary skill in the art would reasonably construe the amount taught by Badman be essentially be the same or obvious substitute for what’s claimed.
The U.S. patent claims do not teach primary biliary cholangitis-associated cholestatic pruritus in a subject suffering from primary biliary cholangitis during treatment of the primary biliary cholangitis where the subject was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid.
Badman teaches a method a method for preventing, delaying or treating a liver disease or disorder including, but not limited to primary biliary cirrhosis, in a patient in need therefor, comprising administering a therapeutically effective amount of
i) a FXR agonist, e.g., 2-[3-({5-cyclopropyl-3-[2-(trifluoromethoxy) phenyl]-1,2-oxazol-4-yl} methoxy)-8-azabicyclo [3.2.1] octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid and of
ii) seladelpar as an additional therapeutic agent, each of the components of the combination being administered simultaneously or sequentially and, in any order, or separate. (See claims 14 and 1-4.) Components (i) and (ii) can be administered together, one after the other or separately in one combined unit dose form or in two separate unit dose forms. (See paragraph [0048].) Another name for primary biliary cirrhosis is primary biliary cholangitis. The daily administration reads on once a day. Moreover, Badman teaches “combination” refers to either a fixed combination in one unit dosage form (e.g., capsule, tablet, or sachet), free (i.e. non-fixed) combination, or a kit of parts for the combined administration where a FXR agonist of the present invention and one or more “combination partner” (i.e. the additional therapeutic agent, such as e.g. seladelpar or a pharmaceutically acceptable salt or solvate thereof) may be administered independently at the same time or separately within time intervals, especially where these time intervals allow that the combination partners show a cooperative, e.g. synergistic effect. (See paragraph 0097.) The route of administration is oral. (See paragraph [0115].) Badman also teaches seladelpar is to be administered at a dose in a range of about 2 mg, about 5 mg/day, about 10 mg/day, about 20 mg/day or about 50 mg, orally. (See paragraph [0167].) Additionally, Badman teaches the time interval between administration of the FXR agonist and of the additional therapeutic agent may vary from a few minutes to a few days, e.g., a few minutes, e.g., a few hours, e.g., 1 day to 1 week. (See paragraph [0136].) The fact that the time interval for the separate administration can be 1 day to 1 week of administration of the combination and in separate unit doss form, one can reasonably interpret the administration of saledalpar separately in its own unit dose form to meet the consisting of language. Badman teaches UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond. Since May 2016, another molecule has been approved in the US for the treatment of PBC, when combined with UDCA for primary biliary cholangitis (PBC) in adult patients with an inadequate response to UDCA, or as a single therapy in adults unable to tolerate UDCA. Lastly, Badman teaches the salt of seladelpar is Lysine (L-lysine) salt. (See paragraph [0028].)
Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, or hereditary pediatric cholestatic disorders and may accompany, although less frequently, many other liver diseases. (See Abstract.) Moreover, Beuers teaches
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Karon teaches the investigational peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis. (See first paragraph.) Moreover, Karon teaches primary biliary cholangitis, an important cause of end-stage liver disease, is initially associated with fatigue and pruritus and often responds inadequately to first-line treatment with ursodeoxycholic acid. MBX-8025 selectively activates the peroxisome proliferator–activated receptor delta, a nuclear receptor that regulates genes involved in lipid storage and transport. In prior studies, MBX-8025 decreased serum alkaline phosphatase (ALP) levels and seemed well tolerated in healthy volunteers and patients with dyslipidemia, the investigators noted. (See third paragraph.)
Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment. (See table 3 and the last paragraph of the left column of page 2052.).
Bergasa teaches cholestasis is defined as impaired secretion of bile. Pruritus is a complication of cholestasis including that associated with mutations in genes that code for transporters in the hepatocyte and from inflammatory liver diseases. (See first paragraph.)
Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. (Seven paragraph under Section 6.6.3.)
It would been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method of the U.S. patent claims that can include seladelpar lysine dihydrate salt as monotherapy by including a subject was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid to treat cholestatic pruritus to give Applicant’s claimed invention. One would have been motivated to so, because Badman teaches seladelpar as a PPAR-δ agonist that can treat various liver diseases including primary biliary cirrhosis and also teaching that UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond, and as a single therapy in adults unable to tolerate UDCA, because Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, because Karon teaches peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis, because Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment, and lastly because Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. One would reasonably expect the method of the U.S. patent claims to be effective for treating primary biliary cholangitis and its associated symptom cholestatic where the subject was previously on a stable and intolerant to ursodeoxycholic acid with success.
Claims 25-50 are rejected on the ground of non-statutory double patenting as being un-patentable over claims 1-16 of U.S. Patent No. 10,272,058B2 in view of Badman (US2019/0076500 A1), Beuers (Hepatology, 2014;60:399-407), Karon et al (MDedge, HCV Hub, November 11, 2016), Vrins et al (Journal of Lipid Research Volume 50, 2009), and Bergasa et al (CRC Press/Taylor & Francis; 2014).
The U.S. patent claims teach a method of treating primary sclerosing cholangitis by administering seladelpar or a salt thereof, where the daily dose of seladelpar or a salt thereof is 5 mg and 10 mg, when the dose is calculated as seladelpar, see claims 1 and 9. The seladelpar or a salt thereof is seladelpar L-lysine dihydrate salt, see claim 2. The seladelpar or a salt thereof is administered orally once/day, see claims 1-16. The claimed amount equivalent to 5 mg/day and the 10 mg/day does not confer a meaningful distinction, as no specialized equivalence is defined. Thus, a person of ordinary skill in the art would reasonably construe the amount taught by Badman be essentially be the same or obvious substitute for what’s claimed.
The U.S. patent claims do not teach primary biliary cholangitis-associated cholestatic pruritus in a subject suffering from primary biliary cholangitis during treatment of the primary biliary cholangitis where the subject was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid.
Badman teaches a method a method for preventing, delaying or treating a liver disease or disorder including, but not limited to primary biliary cirrhosis, in a patient in need therefor, comprising administering a therapeutically effective amount of
i) a FXR agonist, e.g., 2-[3-({5-cyclopropyl-3-[2-(trifluoromethoxy) phenyl]-1,2-oxazol-4-yl} methoxy)-8-azabicyclo [3.2.1] octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid and of
ii) seladelpar as an additional therapeutic agent, each of the components of the combination being administered simultaneously or sequentially and, in any order, or separate. (See claims 14 and 1-4.) Components (i) and (ii) can be administered together, one after the other or separately in one combined unit dose form or in two separate unit dose forms. (See paragraph [0048].) Another name for primary biliary cirrhosis is primary biliary cholangitis. The daily administration reads on once a day. Moreover, Badman teaches “combination” refers to either a fixed combination in one unit dosage form (e.g., capsule, tablet, or sachet), free (i.e. non-fixed) combination, or a kit of parts for the combined administration where a FXR agonist of the present invention and one or more “combination partner” (i.e. the additional therapeutic agent, such as e.g. seladelpar or a pharmaceutically acceptable salt or solvate thereof) may be administered independently at the same time or separately within time intervals, especially where these time intervals allow that the combination partners show a cooperative, e.g. synergistic effect. (See paragraph 0097.) The route of administration is oral. (See paragraph [0115].) Badman also teaches seladelpar is to be administered at a dose in a range of about 2 mg, about 5 mg/day, about 10 mg/day, about 20 mg/day or about 50 mg, orally. (See paragraph [0167].) Additionally, Badman teaches the time interval between administration of the FXR agonist and of the additional therapeutic agent may vary from a few minutes to a few days, e.g., a few minutes, e.g., a few hours, e.g., 1 day to 1 week. (See paragraph [0136].) The fact that the time interval for the separate administration can be 1 day to 1 week of administration of the combination and in separate unit doss form, one can reasonably interpret the administration of saledalpar separately in its own unit dose form to meet the consisting of language. Badman teaches UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond. Since May 2016, another molecule has been approved in the US for the treatment of PBC, when combined with UDCA for primary biliary cholangitis (PBC) in adult patients with an inadequate response to UDCA, or as a single therapy in adults unable to tolerate UDCA. Lastly, Badman teaches the salt of seladelpar is Lysine (L-lysine) salt. (See paragraph [0028].)
Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, or hereditary pediatric cholestatic disorders and may accompany, although less frequently, many other liver diseases. (See Abstract.) Moreover, Beuers teaches
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Karon teaches the investigational peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis. (See first paragraph.) Moreover, Karon teaches primary biliary cholangitis, an important cause of end-stage liver disease, is initially associated with fatigue and pruritus and often responds inadequately to first-line treatment with ursodeoxycholic acid. MBX-8025 selectively activates the peroxisome proliferator–activated receptor delta, a nuclear receptor that regulates genes involved in lipid storage and transport. In prior studies, MBX-8025 decreased serum alkaline phosphatase (ALP) levels and seemed well tolerated in healthy volunteers and patients with dyslipidemia, the investigators noted. (See third paragraph.)
Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment. (See table 3 and the last paragraph of the left column of page 2052.).
Bergasa teaches cholestasis is defined as impaired secretion of bile. Pruritus is a complication of cholestasis including that associated with mutations in genes that code for transporters in the hepatocyte and from inflammatory liver diseases. (See first paragraph.)
Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. (Seven paragraph under Section 6.6.3.)
It would been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method of the U.S. patent claims that can include seladelpar lysine dihydrate salt as monotherapy by including a subject was previously on a stable and recommended dose of, or intolerant to, ursodeoxycholic acid to treat cholestatic pruritus to give Applicant’s claimed invention. One would have been motivated to so, because Badman teaches seladelpar as a PPAR-δ agonist that can treat various liver diseases including primary biliary cirrhosis and also teaching that UDCA (ursodeoxycholic acid) halts progression in many patients, but in about 30-40% of the population do not respond, and as a single therapy in adults unable to tolerate UDCA, because Beuers teaches pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, because Karon teaches peroxisome proliferator–activated receptor delta agonist MBX-8025 exhibited a “striking anticholestatic effect” without causing pruritus in a phase II trial of 35 patients with primary biliary cholangitis, because Vrins teaches PPAR-δ activation led to a higher bile flow and a higher bile salt secretion rate both with and without ezetimibe treatment, and lastly because Bergasa also teaches substances that under physiological conditions are excreted in bile accumulate in body tissues as a result of cholestasis and may stimulate peripheral pruriceptive neurons, providing a peripheral component to the pruritus. In addition, the constant peripheral stimulation may also lead to central sensitization for itch. One would reasonably expect the method of the U.S. patent claims to be effective for treating primary biliary cholangitis and its associated symptom cholestatic where the subject was previously on a stable and intolerant to ursodeoxycholic acid with success.
Applicant’s argument
Applicant argument that the patent claims do not recite treating cholestatic pruritus. As
discussed above, the cited refences does not teach this feature, and at least for this reason, the instant claims 25-50 are patentably distinct from claims of the U.S. Patent. Applicant respectfully requests withdrawal of the rejection.
Examiner’s response
In response, the Examiner finds Applicant’s argument not persuasive. The earlier U.S. patent claims, in combination with the cited references render the present claims obvious. The prior patent claims cover related treatments for PBC. A person of ordinary skill in the art considering the known prior art references and the earlier claims, would have found it obvious to extend the treatment scope to cholestatic pruritus. Thus, the present claims are merely an obvious variation and not patentably distinct.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEAN P CORNET whose telephone number is (571)270-7669. The examiner can normally be reached on Monday-Thursday from 7.00am-5.30pm.
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, Amy L Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JEAN P CORNET/Primary Examiner, Art Unit 1628 A method of treating cholestatic pruritus in a subject in need intolerant
ursodeoxycholic acid, the method comprising orally administering seladelpar or a salt thereof as a monotherapy to the subject in an amount equivalent to 5 mg/day or 10 mg/day of seladelpar