Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Pursuant to the preliminary amendment dated 9/8/2023, claims 1-3, 5, 7, 9, 11, 13, 15, 19-22, 25, 26, 29, 30, 33, 36 and 39 are cancelled and claims 4, 6, 8, 10, 12, 14, 16, 17, 23, 27, 28, 31, 34, 37, 38 and 40 are amended. No claims are newly added.
Claims 4, 6, 8, 10, 12, 14, 16-18, 23, 24, 27, 28, 31, 32, 34, 35, 37, 38 and 40 are pending in the instant application and are examined on the merits herein.
Priority
The application is a National Stage entry of PCT/CA2022/050358 filed on 3/10/2022, which claims priority to provisional application 63/159289 filed on 3/10/2021.
Information Disclosure Statement
The information disclosure statements (IDS) dated 11/22/2024 and 1/28/2025 comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609, except where noted. Accordingly, the IDS documents have been placed in the application file and the information therein has been considered as to the merits.
Claim Rejections - 35 USC § 112
The following is a quotation 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.
Claims 4, 6, 8, 10, 12, 14, 16-18, 23, 24, 27 and 28 are rejected under 35 U.S.C. 112(a), because the specification, while being enabling for preventing, alleviating, ameliorating or palliating the claimed conditions, does not reasonably provide enablement for treating the claimed conditions. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. With respect to the claimed method, attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. All of the Wands factors have been considered and those most relevant to the cited claims are discussed below. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below. Nature of the invention: The rejected invention is drawn to a method for treating or preventing prion diseases and/or brain diseases, disorders or conditions that benefit from reduced levels of the cellular prion protein (PrPᶜ) and/or altered levels of NKA alpha subunits. Relative skill of those in the art: The relative skill of those in the art is high. Breadth of claims: The claims are broad with respect to the concepts of treatment of the claimed conditions. The full scope of the claims encompasses the entire definition of treatment as defined at ¶0064-0066 of the specification, “The term "to treat", treating" or "treatment" as used herein and as is well understood in the art, means an approach for obtaining beneficial or desired results, including clinical results. Beneficial or desired clinical results include, but are not limited to alleviation or amelioration of one or more symptoms or conditions, diminishment of extent of disease, stabilized (i.e. not worsening) state of disease, preventing spread of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, diminishment of the reoccurrence of disease, and remission (whether partial or total), whether detectable or undetectable. "Treating" and "treatment" can also mean prolonging survival as compared to expected survival if not receiving treatment. "Treating" and "treatment" as used herein also include prophylactic treatment…"Palliating" a disease, disorder or condition means that the extent and/or undesirable clinical manifestations of a disease, disorder or condition are lessened and/or time course of the progression is slowed or lengthened, as compared to not treating the disorder. The term "prevention" or "prophylaxis", or synonym thereto, as used herein refers to a reduction in the risk or probability of a patient becoming afflicted with prion diseases and/or other brain diseases, disorders or conditions that benefit from reduced levels of the cellular prion protein (PrPc), or manifesting a symptom associated with prion diseases and/or other brain diseases, disorders or conditions that benefit from reduced levels of the cellular prion protein (PrPc).” (Emphasis added) The claims are also broad with respect to the nature of the prion diseases and/or brain diseases, disorders or conditions that benefit from reduced levels of the cellular prion protein (PrPᶜ) and/or altered levels of NKA alpha subunits, which include, but are not limited to, rapid-onset dystonia parkinsonism, hemiplegia, autosomal dominant cone-rod dystrophy, Angelman's syndrome, SOD-1 forms of amyotrophic lateral sclerosis, forms of ataxia, epilepsy, mania, scrapie in sheep, chronic wasting disease in deer elk and moose, bovine spongiform encephalopathy in cattle, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia in humans and Alzheimer's disease, as per claims 24, 27 and 28.
Amount of guidance/Existence of working examples:
The working examples (Examples 1-3) provide detailed studies on administering the claimed oleandrin derivatives, showing effectiveness in reducing PrPc levels and altering levels of Na,K-ATPase subunits, which correlates to expected alleviation, amelioration, palliation or reduction in the risk or probability of a patient becoming afflicted with prion diseases and/or brain diseases, disorders or conditions that benefit from reduced levels of the cellular prion protein (PrPᶜ) and/or altered levels of NKA alpha subunits. However, there is no data in the specification demonstrating that administering the claimed oleandrin derivatives would be effective to achieve total remission of any prion disease and/or brain disease, disorder or condition that benefit from reduced levels of the cellular prion protein (PrPᶜ) and/or altered levels of NKA alpha subunits. State of the prior art/Predictability or unpredictability of the art: Arafah et al. (Biomedicines, 2023, PTO-892) discloses that currently, Alzheimer’s disease is effectively incurable because the medications that are currently available have a negligible impact on the severity and progression of the disease. (Sec. 1) Thus, one of skill in the art would not expect that treatment of any prion diseases and/or brain diseases, disorders or conditions that benefit from reduced levels of the cellular prion protein (PrPᶜ) and/or altered levels of NKA alpha subunits, would be capable of achieving total remission, based on the disclosure of Arafah et al.
Quantity of experimentation: One of skill in the art would have to conduct a myriad number of experiments comprising trial and error administration of the claimed oleandrin derivatives, to both healthy individuals and individuals having a representative number of prion diseases and/or brain diseases, disorders or conditions that benefit from reduced levels of the cellular prion protein (PrPᶜ) and/or altered levels of NKA alpha subunits, to determine if the claimed method can be used in the fully claimed scope for treatment of, including total remission of, such diseases/conditions. Genetech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”. Therefore, in view of the Wands factors as discussed above, e.g., the breadth of the claims, the amount of guidance provided, the state/unpredictability of the art and the lack of working examples, one of skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims, with no assurance of success.
Allowable Subject Matter
With respect to claims 31, 32, 34, 35, 37, 38 and 40, the compounds claimed therein are found to be allowable. The closest applicable prior art is that of Chen et al. (Fitoterapia, 2016, IDS) Chen discloses the following compounds: (Schemes 1, 2)
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However, the compound of Chen are explicitly excluded by the provisions in the instant claims regarding the relationship between the variables X, R1, R2 and R3. There is no suggestion within Chen, or the prior art at large, to modify Chen to arrive at the instantly claimed compounds.
With respect to claims 4, 6, 8, 10, 12, 14, 16-18, 23, 24, 27 and 28, the narrower scope of a method of ameliorating, alleviating, palliating, or preventing prion diseases and/or brain diseases, disorders or conditions that benefit from reduced levels of the cellular prion protein (PrPᶜ) and/or altered levels of NKA alpha subunits, by administering the claimed oleandrin derivatives would be allowable. The rationale for the allowability of the narrower scope method is as follows: The closest applicable prior art is Addington et al. (US 2011/0172172 A1, IDS). Addington discloses a method for treating a neurological disease or disorder having an etiology associated with altered Na,K-ATPase activity with a composition comprising cardiac glycoside, specifically oleandrin, the method comprising determining that the subject has a neurological
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oleandrindisease or disorder having an etiology associated with altered Na,K-ATPase alpha-3 isoform to alpha-1 isoform subunit ratio or associated with altered Na,K-ATPase activity. (Claims 3, 43) Addington discloses that the neurological disorder may be selected from Huntington's disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, bovine spongiform encephalopathy, multiple sclerosis, diabetic neuropathy, autism and juvenile neuronal ceroid lipofuscinosis. (¶0039) Oleandrin is excluded as an active agent by the instant claims, however, there are known cardiac glycosides, as per Chen above, that fall within the scope of the administered compounds of claim 4. Prima facie one would expect the cardiac glycosides of Chen to be effective in the method of Addington. However, the instant specification presents evidence of unexpected results where the claimed compounds were found to be surprisingly superior when compared to oleandrin. Particularly, oleandrin was inferior to the claimed compounds with respect to brain bioavailability and toxicity, as well as ability to reduce levels of the prior protein PrPc. (¶0088, 0228-0230) Therefore, a method with narrowed scope of ameliorating, alleviating, palliating, or preventing prion diseases and/or brain diseases, disorders or conditions that benefit from reduced levels of the cellular prion protein (PrPᶜ) and/or altered levels of NKA alpha subunits, would not be obvious over Addington, in view of Chen, due to a showing of unexpected results, which overcomes a prima facie case of obviousness.
Conclusion
Claims 31, 32, 34, 35, 37, 38 and 40 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DALE R MILLER whose telephone number is (571) 272-6146. The examiner can normally be reached on M-F 7:00 AM – 3:30 PM EST.
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/DALE R MILLER/Primary Examiner, Art Unit 1693