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 national stage entry of PCT/JP2023/005654 filed on 02/17/2023. Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Japan on February 22, 2022.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election without traverse of Group II (claims 4 and 5) drawn to a method of treating, improving, or preventing a cancer comprising administering an ATP8B2 inhibitor to a subject in the reply filed on August 28, 2026 is acknowledged. Applicant’s election without traverse of cervical cancer as a species of cancer and compound 3, 9-(1-octylcyclopropyl)nonan-1-ol as a species of an ATP8B2 inhibitor in the reply filed on August 28, 2026 is also acknowledged.
Claim 3 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 4 and 5 are currently presented for examination.
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 4 and 5 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 enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The specification does not provide sufficient information to show that compound 3, 9-(1-octylcyclopropyl)nonan-1-ol or any other ATP8B2 inhibitor can be used in a method of treating, improving, or preventing ovarian cancer or any other cancer.
The instant specification fails to provide information that would allow the skilled artisan to practice the instant invention without undue experimentation. Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art, the relative skill of those in the art, and the amount of experimentation necessary. 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: Claims 4 and 5 of the instant application are drawn to a method of treating, improving, or preventing a cancer such as ovarian cancer, comprising administering an ATP8B2 inhibitor, such as compound 3, 9-(1-octylcyclopropyl)nonan-1-ol, to a subject.
Breadth of the claims: The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims. The rejected claims are extremely broad. Applicant claims that in addition to compound 3, 9-(1-octylcyclopropyl)nonan-1-ol, any ATP8B2 inhibitor can be used to not only improve and treat any cancer, but also prevent any cancer including ovarian cancer. Thus the claims are broad as they encompass treating and preventing not only ovarian cancer but any type of cancer comprising the administration of any compound or agent that inhibits ATP8B2.
Guidance of the Specification/Working Examples: In the instant specification, Applicant states that an ATP8B2 inhibitor is not particularly limited as long as it inhibits ATP8B2 directly or indirectly, wherein examples of the ATP8B2 inhibitor include compounds, antibodies, proteins, peptides, DNA aptamers, and RNA aptamers that bind to ATP8B2 and suppress the activity of ATP8B2. The ATP8B2 inhibitor may inhibit ATP8B2 through suppressing the expression of the ATP8B2 gene such as siRNA, antisense nucleic acid, or the like. Applicant further states that the ATP8B2 inhibitor is preferably a compound, such as an aliphatic alcohol, which is specifically 9-(1- octylcyclopropyl)nonan-1-ol, (S)-3-(9-(1-octylcyclopropyl)nonyl)oxy)propane-1,2-diol, or a pharmacologically acceptable salt thereof, or the like. Thus, numerous agents can be selected as an ATP8B2 inhibitor. Applicant’s data as it pertains to the claimed invention can be found in Examples 1-4 on pages 15-24 of the instant specification. Applicant demonstrates using siRNA which suppresses the expression of ATP8B2 in cervical cancer cells that TNBS-modified plasmalogen is increased and phosphorylated AKT is decreased. Applicant also demonstrates that growth was inhibited in these cells. Applicant further tests aliphatic alcohol compounds for their ability to decrease phosphorylated AKT in cervical cancer cells. Applicant demonstrates that these compounds reduced phosphorylated AKT expression in cervical cancer cells. Applicant merely hypothesize that these compounds reduce phosphorylated AKT as a result of inhibition of ATP8B2 (see page 19 of specification). Applicant does not provide any data which demonstrates that the effects observed on phosphorylated AKT are due to the inhibition of ATP8B2 by the aliphatic alcohol compounds. No evidence is provided demonstrating that compound 3 or any other aliphatic alcohol compound actually inhibits ATP8B2. No evidence is provided showing the inhibition of cancer cell growth in vitro or the decrease in tumor size in vivo using the claimed aliphatic alcohols. Furthermore, Applicant has not provided any evidence that the claimed compounds are useful in treating cancer. Applicant has not provided any evidence suggesting that these data will lead to any practical application in the treatment or prevention of any cancer. The treatment of cancer is complex and requires rigorous testing to confirm effective treatment. Thus Applicant’s data is merely speculative and does not provide any evidence that the claimed compounds or any other agent that inhibits ATP8B2 will result in the effective treatment or prevention of cervical cancer or any other cancer. Thus, the specification fails to provide sufficient evidence to support treating, improving, or preventing a cancer such as ovarian cancer, comprising administering an ATP8B2 inhibitor, such as compound 3, 9-(1-octylcyclopropyl)nonan-1-ol, to a subject as recited in the instant claims.
State of the Art: Prior to the effective filing date of the claimed invention, there were no known ATP8B2 inhibitors in clinical use for the treatment of any cancer or any other disease or disorder. Moreover, a thorough search of the prior art did not find any known compounds that were useful for inhibiting ATP8B2. Prior to the effective filing date of the claimed invention, the use of P4-ATPases in disease was underdeveloped. Andersen et al. (Frontiers in Physiology, Volume 7, July 2016, pages 1-23) teaches that P-type ATPases constitute a family of membrane proteins that utilize the energy from ATP hydrolysis to transport ions and lipids across biological membranes (page 2). P4-ATPases are only found in eukaryotes and the human genome encodes 14 P4-ATPases that are organized into five classes with each class having multiple members (page 2). Class 1b includes ATP8B1, ATP8B2, ATP8B3, ATP8B4 (page 2). Andersen et al. teaches that prior to the effective filing date of the claimed invention, while ATP8B2 was known, its association with a particular disease or disorder was unknown (page 3 Table 1). Andersen et al. teaches that several P4-ATPases including ATP8B1, ATP8B2, and ATP8B4 can associate with either CDC50A or CDC50B, but the physiological consequence of this dual specificity, however, remains to be determined (page 4). Thus the state of the art teaches that prior to the effective filing date of the claimed invention the role of ATP8B2 and its implications in disease was unknown and just beginning to emerge. Thus the state of the art prior to the effective filing date of the claimed invention fails to support the use of any ATP8B2 inhibitor compound or agent in the treatment or prevention of any cancer as claimed in the instant application.
Predictability/Unpredictability in the Art: It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instant claimed invention is highly unpredictable since one skilled in the art would recognize that the recitation encompasses the treatment or prevention of cancer, which includes a great number of cancer types with different etiologies, comprising the administration of any agent that inhibits ATP8B2 including compounds, antibodies, proteins, peptides, DNA aptamers, and RNA aptamers that bind to ATP8B2 and suppress the activity of ATP8B2. Thus, the skilled artisan would view that the treatment of all disorders/diseases encompassed by the claims, by administering all compounds or agents encompassed by the claims, is highly unpredictable since the instant specification does not provide sufficient evidence to support the instant claims and the state of the art does not support the instant claims.
Moreover, one of skill in the art would recognize that it is highly unpredictable in regard to therapeutic effects, side effects and toxicity generated by administering all agents encompassed by the claims for treating all disorders/diseases encompassed by the claims.
The Quantitation of Experimentation Required: In order to practice Applicant’s invention, it would be necessary for one to design and conduct an exhaustive amount of complex experiments to demonstrate that any ATP8B2 inhibitor can be used to not only improve and treat any cancer, but also prevent any cancer including ovarian cancer. One would need to perform extensive pharmacokinetic and pharmacological experiments to determine efficacy, potency, etc. for each agent and determine if any cancer is treatable. Therefore, in order to practice the claimed invention, the amount of experimentation required would be considered undue and burdensome.
In conclusion, 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 limitations of general ideas that may or may not be workable.” A method of treating, improving, or preventing any cancer including ovarian cancer, comprising administering any ATP8B2 inhibitor, including compound 3, 9-(1-octylcyclopropyl)nonan-1-ol is not enabled by the instant specification.
Conclusion
Claims 1 and 2 are canceled. Claim 3 is withdrawn. Claims 4 and 5 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM
