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 .
Status of the Application
Claims 1-21 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 09/02/2025 are acknowledged. Claims under consideration in the instant office action are claims 1-21.
Applicants' arguments, filed 09/02/2025, have been fully considered and they are deemed to be persuasive regarding the rejection of claims 1-21 under 35 U.S.C. 103 has been withdrawn since Schreiber et al. is not considered prior art based on Applicant’s Declaration. The rejection of claims 12 and 15 under 35 U.S.C. 112 has been withdrawn due to Applicant’s amendments. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3-6, 9, 12-13, 15-17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Schenk et al. (Nephron-specific knockout of TMEM16A leads to reduced number of glomeruli and albuminuria, American Journal of Renal Physiology, 2018, 315, pp. F1777-F1786) in view of Miner et al. (Drug repurposing: The Anthelmintics Niclosamide and Nitazoxanide Are Potent TMEM16A Antagonists That Fully Bronchodiiate Airways, Frontiers in Pharmacology, 2019, 10, pp. 1-34, as disclosed in IDS).
Schenk et al. is drawn towards the role of the TMEM16A protein in kidney function (see abstract). Schenk et al. teaches that “TMEM16A is localized in the primary cilium of epithelial cells and can mediate cilia length and differentiation. It has been shown that TMEM16A promotes renal cyst growth via induction of chloride secretion and pro-proliferative effects on the cyst lining epithelium.” (pg. F1777, right column, first paragraph). Schenk et al. thus teaches that inhibition of the TMEM16A protein results can result in a reduction of renal cysts, which are characteristic in polycystic kidney disease.
Schenk et al. does not teach administering niclosamide for the treatment of PKD. Schenk et al. does not teach co-administering an agent such as an antiinfective agent.
Miner et al. is drawn towards TMEM16 antagonist activity of niclosamide and nitazoxanide (see abstract). Miner et al. teaches “The anthelmintics niclosamide, nitazoxanide, and related compounds were identified as potent TMEM16A antagonists that blocked away smooth muscle depolarization and contraction…For the first time we identify TMEM16A as a molecular target for these drugs” (see abstract).
It would have been obvious to one of ordinary skill in the art to administer niclosamide for the treatment of PKD, as suggested by Miner et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since niclosamide, as a potent TMEM16A antagonist as taught by Miner et al., can be administered to inhibit renal cyst growth in PKD via TMEM16A knockout as taught by Schenk et al., with a reasonable expectation of success absent evidence of criticality of the particular steps.
It would have been obvious to one of ordinary skill in the art to co-administer an agent such as an antiinfective agent, as suggested by Miner et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since it is prima facie obvious to combine components known for the same purpose for their combined additive effects, with a reasonable expectation of success absent evidence of criticality of the particular formulation. Additionally, “[T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Therefore, it would have been prima facie obvious to combine niclosamide and nitazoxanide in a composition cojointly to treat PKD.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Schenk et al. (Nephron-specific knockout of TMEM16A leads to reduced number of glomeruli and albuminuria, American Journal of Renal Physiology, 2018, 315, pp. F1777-F1786) and Miner et al. (Drug repurposing: The Anthelmintics Niclosamide and Nitazoxanide Are Potent TMEM16A Antagonists That Fully Bronchodiiate Airways, Frontiers in Pharmacology, 2019, 10, pp. 1-34, as disclosed in IDS) as applied to claims 1, 3-6, 9, 12-13, 15-17, and 20 above, and further in view of Cnossen (Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management, Orphanet Journal of Rare Diseases 2014, 9:69, pp. 1-13).
The teachings of Schenk et al. and Miner et al. are presented above.
Schenk et al. and Miner et al. do not teach further treating polycystic liver disease (PLD). Cnossen teaches “Polycystic liver disease (PLD) is the result of embryonic ductal plate malformation of the intrahepatic biliary tree. The phenotype consists of numerous cysts spread throughout the liver parenchyma. Cystic bile duct malformations originating from the peripheral biliary tree are called Von Meyenburg complexes (VMC). In these patients embryonic remnants develop into small hepatic cysts and usually remain silent during life. Symptomatic PLD occurs mainly in the context of isolated polycystic liver disease (PCLD) and autosomal dominant polycystic kidney disease (ADPKD). In advanced stages, PCLD and ADPKD patients have massively enlarged livers which cause a spectrum of clinical features and complications.” (see abstract).
It would have been obvious to one of ordinary skill in the art to further treat PLD, as suggested by Cnossen, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since the cyst formation that occurs in PLD can be targeted by niclosamide via TMEM16A knockout as taught by Schenk et al. and Miner et al., with a reasonable expectation of success absent evidence of criticality of the particular steps.
Claims 7-8, 10-11, 14, 18-19, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Schenk et al. (Nephron-specific knockout of TMEM16A leads to reduced number of glomeruli and albuminuria, American Journal of Renal Physiology, 2018, 315, pp. F1777-F1786) and Miner et al. (Drug repurposing: The Anthelmintics Niclosamide and Nitazoxanide Are Potent TMEM16A Antagonists That Fully Bronchodiiate Airways, Frontiers in Pharmacology, 2019, 10, pp. 1-34, as disclosed in IDS) as applied to claims 1, 3-6, 9, 12-3, 15-17, and 20 above, and further in view of Al-Hadiya (Niclosamide: Comprehensive Profile, Profiles of Drug Substances, Excipients and Related Methodology, 2005, 32, pp. 67-96).
The teachings of Schenk et al. and Miner et al. are presented above.
Schenk et al. and Miner et al. do not teach administering niclosamide, wherein said compound is administered in an amount of from 10 mg per day to 800 mg per day, or wherein said compound is administered once every 4-8 h, once daily, or once weekly.
Al-Hadiya is drawn towards a comprehensive profile of niclosamide. Al-Hadiya teaches that niclosamide can be administered orally as a single dose in an amount of 1-2 g (pg. 93, 6.4. Dosing Information). Al-Hadiya teaches that niclosamide was compatible with a majority of common tablet excipients (pg. 9, top paragraph).
It would have been obvious to one of ordinary skill in the art to administer niclosamide, wherein said compound is administered in an amount of from 10 mg per day to 800 mg per day, or wherein said compound is administered once every 4-8 h, once daily, or once weekly, as suggested by Al-Hadiya, and produce the instant invention.
With regards to the limitation claimed in instant claims 7 and 18, which claims a dosage of from 10 mg per day to 800 mg per day, Cnossen does not specifically teach the exact amounts claimed in instant claims 7 and 18. However, it would be within the skill of an ordinary artisan to be able to modify the dosage in order to obtain the desired bioavailability of niclosamide It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Conclusion
Claims 1-21 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW P LEE whose telephone number is (571)270-1016. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ANDREW P LEE/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691