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 application under 35 U.S.C. § 371 of International Application No. PCT/JP2022/024408, filed 06/17/2022, which claims the priority benefit of PCT Application No. PCTJP2021023645, filed 06/22/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/26/2026, and 12/22/2023 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-7 with a species election of (1R,3S,5Z)-5-[(2E)-2-[(2R,3S)-3-[2-(3-Hydroxy-3-methylbutoxy)phenyl]-2-methylcyclo- hexylidene]ethylidene]-4-methylene-1,3-cyclohexanediol (CAS RN 2885231-14-9) in the reply filed on 04/29/2026 is acknowledged.
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Status of the Application
Claim1-13 are pending. Claims 4-13 have been amended. Claims 8-13 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 4-7 have been withdrawn from further consideration by examiner as being drawn to a non-elected species for the following reasons, claim 4 is drawn to the compound of formula (2) which differs from applicants elected compound at Z which is defined as a halogen atom or a group represented by Formula (3) (below) and therefore withdrawn from consideration. Claim 5 is drawn to the compound of formula (4) which differs from applicants elected species by the COO group connected to R9 and Z which is defined as a halogen atom or a group represented by Formula (3) (below) and is therefore withdrawn from consideration. Claim 6 is drawn to the compound of formula (5) which differs from applicants elected compound by the inclusion of an OH group attached to the phenyl ring and at Z which is defined as a halogen atom or a group represented by Formula (3) (below) and is therefore withdrawn from consideration. Claim 7 is drawn to the compound of formula (6) which differs from applicants elected compound by the =O group attached to the hexane ring and at the W group which is defined as a protecting group which may be a silyl ether protecting group, such as TMS (trimethylsilyl), TES (triethylsilyl), or TBS (tert-butyldimethylsilyl) as defined by the specification [0065] and is therefore withdrawn from consideration. Claims 1-3 are examined herein insofar as they read on the elected invention and species.
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Applicants formula (2) (Left) Applicants formula (4) (Right)
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Applicants formula (5) (Left) Applicants formula (6) (Right)
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Applicants formula (3) (above)
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Abstract
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because the use of the term “etc” in lines 4, 6, and 10 for the Y, R2 and R5 groups in formula 1 are indefinite. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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 2-3 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification [0054], while being enabling for treating a disease responsive to active vitamin D3 of osteoporosis, rickets, chronic hypocalcemia, renal osteodystrophy, secondary hyperparathyroidism, psoriasis, or cancer, does not reasonably provide enablement for preventing the onset of osteoporosis, rickets, chronic hypocalcemia, renal osteodystrophy, secondary hyperparathyroidism, psoriasis, or cancer. 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.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." In In re Wands, 8 USPQ2d 1400 (1988), the factors to be considered in determining whether a disclosure meets the enablement requirement are as follows:
1. The nature of the invention
2. The state of the prior art
3. The predictability or lack thereof in the art
4. The amount of direction or guidance present
5. The presence or absence of working examples
6. The breadth of the claims
7. The quantity of experimentation needed, and
8. The level of skill in the art
The Nature of the Invention and Breadth of the Claims
Claims 2 and 3 is drawn to a prophylactic or therapeutic agent of a disease responsive to active vitamin D3 of osteoporosis, rickets, chronic hypocalcemia, renal osteodystrophy, secondary hyperparathyroidism, psoriasis, or cancer wherein the prophylactic comprises a compound of formula (1), according to claims 2 and 3.
The State of the Prior Art and the Predictability or lack thereof in the art
As disclosed in the specification below:
[0002] Active vitamin D3 derivatives are used as therapeutic agents for osteoporosis as they act to promote calcium absorption in the small intestine and to regulate bone resorption and bone formation. They are also used for the treatment of secondary hyperparathyroidism with increased parathyroid hormone (PTH) as they have an inhibitory effect on the secretion of PTH. In addition to these activities, they have been found to have immunomodulating activity, cytostatic activity, and cell differentiation activity and have been studied on their use as therapeutic agents for, for example, cancer, psoriasis, rheumatoid arthritis, true diabetes, hypertension, acne, eczema, dermatitis, and other diseases.
[0003] In the conventional art, such active vitamin D3 derivatives useful for the treatment of various diseases are produced in a variety of forms (see, for example, Non-Patent Documents 1 and 2).
[0055] Examples of diseases responsive to active vitamin D3 include osteoporosis, rickets, chronic hypocalcemia, renal osteodystrophy, secondary hyperparathyroidism, psoriasis, and cancer.
However, none of the prior art compounds are reported to completely prevent the onset of any or every disease responsive to active vitamin D3 by promoting calcium absorption in the small intestine and regulating bone resorption, inhibitory effects on the secretion of parathyroid hormone PTH and bone formation and immunomodulating, cytostatic, and cell differentiation activity.
It is noted that pharmacological activity in general is a very unpredictable area. In cases involving physiological activity, such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.” See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The Amount of Guidance Present and Presence/Absence of Working Examples
The only guidance disclosed by the specification regarding preventing the onset of diseases responsive to active vitamin D3 of osteoporosis, rickets, chronic hypocalcemia, renal osteodystrophy, secondary hyperparathyroidism, psoriasis, or cancer is found in [0002]-[0004] and [0054]-[0055]:
[0002] Active vitamin D3 derivatives are used as therapeutic agents for osteoporosis as they act to promote calcium absorption in the small intestine and to regulate bone resorption and bone formation. They are also used for the treatment of secondary hyperparathyroidism with increased parathyroid hormone (PTH) as they have an inhibitory effect on the secretion of PTH. In addition to these activities, they have been found to have immunomodulating activity, cytostatic activity, and cell differentiation activity and have been studied on their use as therapeutic agents for, for example, cancer, psoriasis, rheumatoid arthritis, true diabetes, hypertension, acne, eczema, dermatitis, and other diseases.
[0003] In the conventional art, such active vitamin D3 derivatives useful for the treatment of various diseases are produced in a variety of forms (see, for example, Non-Patent Documents 1 and 2).
[0054] Prophylactic or Therapeutic Agent
There is provided a prophylactic or therapeutic agent including the compound of Formula (1) as an active ingredient. Such a prophylactic or therapeutic agent is effective against diseases responsive to active vitamin D3. The compound of Formula (1) is as described above, and a detailed description thereof will not be repeated here. The term "prophylactic" is intended to include not only preventing the onset of diseases but also delaying the onset of diseases. The term "therapeutic" is intended to include not only eliminating or reducing the symptoms of diseases but also controlling the rate of progression of symptoms.
[0055] Examples of diseases responsive to active vitamin D3 include osteoporosis, rickets, chronic hypocalcemia, renal osteodystrophy, secondary hyperparathyroidism, psoriasis, and cancer.
The specification does not provide any guidance for determining which particular patient population would be susceptible to developing diseases responsive to active vitamin D3. Also lacking are data showing that the compounds are capable of treating all or every disease responsive to active vitamin D3. The time-resolved fluorescence resonance energy transfer (TR-FRET) vitamin D receptor (VDR) coactivator assay results (e.g., Table 1 [0447]) showing binding of the test compound to the vitamin D receptor indicates solely that the compounds can treat the claimed diseases/disorders dependent on vitamin D receptors, not prevent them.
The quantity of experimentation needed, and level of skill in the art
In order to treat every or all diseases responsive to active vitamin D3 and cancer types one would need to precisely identify those subjects with the disease or disorder who are likely to respond to treatment, administer the claimed invention, and demonstrate that administration directly resulted in the subject overcoming the disease or disorder. One skilled in the art would conclude that the guidance in the specification would not have taught one skilled in the art how to treat every or all disease responsive to active vitamin D3 and cancer types using the compounds of formula (1), because there is no guidance for how to select a patient population and no evidence that the claimed compounds can broadly treat every cancer type. Given the lack of guidance in the specification and the lack of success in the prior art, one skilled in the art would find that preventing the claimed diseases or disorders would require experimentation that is unduly burdensome.
This rejection may be overcome by cancelling claims 2 and 3, or specifying which cancer type is being treated from line 3 of claim 3 as well as amending definition of the term prophylactic in the specification language in [0054] to omit the term “preventing” and deleting ‘prophylactic or’ from the claims.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter:
The applicants elected species of formula 1 (1R,3S,5Z)-5-[(2E)-2-[(2R,3S)-3-[2-(3-hydroxy-3-methylbutoxy)phenyl]-2-methylcyclo- hexylidene]ethylidene]-4-methylene-1,3-cyclohexanediol (CAS RN 2885231-14-9) makes a contribution over the closest prior art of record, Reddy (WO-9851678-A1).
Reddy teaches “[i]n other embodiments, therapeutic applications of the vitamin D3 compounds of formulas I and II include treatment of other diseases characterized by metabolic calcium and phosphate deficiencies. Exemplary of such diseases are the following: osteoporosis, osteodystrophy, osteomalacia, rickets, osteitis fibrosa cystica, renal osteodystrophy, osteosclerosis, anti-convulsant treatment, osteopenia, fibrogenesis-imperfecta ossium, 15 secondary hyperparathyrodism,” (pg. 42, lines 10-19). Reddy also discloses the compound of formula I as a cyclic ether vitamin D3 compound which is administered to patients for the growth inhibition of neoplastic cells (pg. 4, lines 30-34), as well as osteoporosis, rickets, secondary hyperparathyroidism, and renal osteodystrophy (pg. 42, lines 10-19). The distinction between applicants compound of formula 1 and the prior art occurs in the structural differences between Applicants formula 1 and Reddy’s formula I wherein a bicyclic ring occurs at the center carbon ring and an oxygen atom in the R3, R4, R5 ring. Reddy does not fairly teach or suggest the structural features of applicants formula 1 to a person of ordinary skill. Therefore, Applicants compound of formula 1, claim 1 is found free of the prior art as of the current record.
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Reddy’s formula I (Left) Applicant’s formula I (Center) Applicant’s elected species (Right)
Conclusion
Claim 1 is allowable, claims 2-3 are rejected.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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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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/E.V./Examiner, Art Unit 1623
/SAMANTHA L SHTERENGARTS/Primary Examiner, Art Unit 1623
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