DETAILED ACTION
Notice of AIA Status
The instant application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ).
If the status of the application as subject to AIA or pre-AIA is incorrect, any correction of the statutory basis (e.g., changing from AIA to pre-AIA ) for a rejection under 35 U.S.C. §§ 102 and/or 103 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.
Status of the Claims
The listing of claims filed 11 April 2025 has been examined.
Claims 1–4, 6, 8, 13, 14, 16, 18, 20, 22, 27, 30, 33, 36, 37, 39, 46, and 48 are pending.
Claims 1, 3, 4, 6, 8, 16, 18, 20, 22, 27, 30, 33, 36, 37, 39, 46, and 48 are currently amended.
Claims 5, 7, 9–12, 15, 17, 19, 21, 23–26, 28, 29, 31, 32, 34, 35, 38, 40–45, 47, and 49–56 are canceled.
Benefit of Earlier Filing Date
The instant application was filed 5 September 2024; is a continuation application of PCT/US2023/064615, filed 17 March 2023, and claims the benefit of an earlier filing date of U.S. Prov. Pat. App. Serial Nos. 63/321,302, filed 18 March 2022; 63/392,878, filed 28 July 2022; and 63/485,657, filed 17 February 2023. Applicant’s claim is acknowledged.
Information Disclosure Statement
An information disclosure statement (IDS) has not been received.
Objections to the Specification
The abstract of the disclosure is objected to because it recites phrases that can be implied (“This disclosure relates to”) and legal phraseology (“comprising”).
Appropriate correction is required.
Examiner recommends starting the sentence: “Ganaxolone derivatives, as well as . . .”
For guidelines for the preparation of patent abstracts, see MPEP § 608.01(b) (Explaining: The abstract should be in narrative form and avoid legal phraseology (e.g., means, said), terms referring to purported merits of the invention (e.g., new, novel), and phrases that can be implied (e.g., The disclosure concerns, The disclosure defined by this invention). The language should be clear and concise, and not repeat information given in the title. It should not compare the invention with the prior art. The abstract is generally limited to a single paragraph within the range of 50 to 150 words in length.).
Claim Rejections - 35 U.S.C. § 112
The following is a quotation of 35 U.S.C. § 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 36 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 36 recites, “a compound selected from Table 1.”
The written description and the claims are separate statutory requirements. Under modern claim practice, claims must stand alone to define an invention. Ex parte Fressola, 27 USPQ2d 1608 (BPAI 1993). Because claim 36 refers to Table 1 rather than providing a chemical name or structure for each compound, one of ordinary skill in the art must refer back to the specification to understand what the claimed invention is.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 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 46 and 48 are rejected under 35 U.S.C. § 112(a) because 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 the claims.
MPEP § 2164.01(a) explains how enablement for the claimed invention can be analyzed:
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.” . . . These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The Wands factors are analyzed with respect to the claimed invention in turn below.
The breadth of the claim is broad in scope, as it extends to treating any disease or disorder (claim 46), including any central nervous system disorder, neurological disorder, or neurodegenerative disorder (claim 48).
The nature of the invention generally relates to the pharmaceutical art and more specifically to derivatives (i.e., prodrugs) of ganaxolone—a drug approved in the U.S. for the treatment of seizures. Ganaxolone is a modulator of gamma-aminobutyric acid (GABA) receptors. (Spec, p.1). Thus, the nature of the invention is sophisticated.
The state of the prior art is developed for ganaxolone—a drug approved in the U.S. for the treatment of seizures. However, the claims extend to treating any disease or disorder (claim 46) and any central nervous system disorder, neurological disorder, or neurodegenerative disorder (claim 48).
Generally, in order to treat a disease, one of skill in the art must identify a biological target for affecting the disease, demonstrate a first drug candidate some way modulates the normal processes of the biological target, and demonstrate that a subject would benefit from such modulation without detrimental side effects. Typically, the process includes in vitro laboratory screening, in vivo testing, and clinical testing. Once that process has been successfully completed by the first drug candidate, subsequent drug candidates can benefit from the established proof of concept if a substantial correlation can be established between the first drug candidate and the subsequent drug candidates.
Examiner is unaware of evidence from that supports a claim for treating any disease or disorder with ganaxolone (claim 46), or any central nervous system disorder, neurological disorder, or neurodegenerative disorder with ganaxolone (claim 48). Thus, the state of the prior art is in its infancy for treating the full scope of the claimed diseases.
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
The level of predictability in the art is generally unpredictable. The relevant art requires each potential drug candidate to be assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18, 24 (CCPA 1970). The more unpredictable an area is the more specific disclosure is necessary to satisfy the statutory requirement. MPEP § 2164.02(II) explains that a correlation between the claimed invention and the evidence provided in an application, along with a correlation between the evidence and the models recognized in the art, are required:
“Correlation” as used herein refers to the relationship between in vitro or in vivo animal model assays and a disclosed or a claimed method of use. An in vitro or in vivo animal model example in the specification, in effect, constitutes a “working example” if that example “correlates” with a disclosed or claimed method invention. If there is no correlation, then the examples do not constitute “working examples.” In this regard, the issue of “correlation” is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. In re Brana, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed. Cir. 1995) (reversing a USPTO decision based on finding that in vitro data did not support in vivo applications).
Further, treatments may be effective for some subjects and ineffective for other subjects. Thus, each candidate for pharmaceutical or veterinary medicine must be evaluated on its own even when a nexus to an existing drug or class of drugs has been established.
The amount of direction provided by the inventor includes a list of diseases that may be included within the scope of the claimed methods and reference to other patent publications that describe other disorders. The specification states the subjects are human. And the specification states the conversion of ganaxolone prodrugs to the active agent is an unpredictable process. (Spec. pp.172–176).
The existence of working examples relate to solubility, stability, and pharmacokinetic studies of the claimed ganaxolone prodrugs. There are no examples demonstrating in vivo activity of the claimed ganaxolone prodrugs for the claimed diseases.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure is extensive, as it includes in vitro and in vivo screening for each specific disease or disorder encompassed by the claims with respect to the claimed ganaxolone prodrugs. As claimed, the scope of such diseases is essentially unbound.
Scope of Enablement Conclusion
In view of the Wands factors discussed above, the disclosure of the instant application does not reasonably enable a person having ordinary skill in the art to use the full scope of the claimed invention. The breadth of the claims is broad in scope; the nature of the invention is sophisticated; the state of the prior art is in its infancy for preventing any disease and for treating most generic classes of disease and specific diseases recited in the claims and ascending for treating cancer, neurodegenerative diseases, and inflammation; the level of skill in the art is high; the pharmaceutical art is unpredictable; the direction provided by the inventor is limited to identifying selective HDAC6 inhibitors and in vitro evaluation; there are no working examples demonstrating in vivo activity against a specific disease with a selective HDAC6 inhibitor; and the quantify of experimentation needed to practice the claimed invention is extensive. Thus, when the evidence is considered as a whole, undue experimentation would be required to practice the full scope of the claimed invention.
Examiner recommends amending claim 46 to recite seizure disorder and the specific epilepsy diseases recited in claim 48; and canceling claim 48.
Claim Rejections - 35 U.S.C. § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
(i) Claims 1, 2, 30, 46, and 48 are rejected under 35 U.S.C. §§ 102(a)(1) and (a)(2) as being anticipated by WO 2015/081170 (“Volkmann”).
Volkmann discloses ganaxolone prodrug compounds according to Formula Ia:
PNG
media_image1.png
310
361
media_image1.png
Greyscale
PNG
media_image2.png
425
531
media_image2.png
Greyscale
(Volkmann, pp.3, 45).
The following compound was indexed in the Registry database:
PNG
media_image3.png
233
481
media_image3.png
Greyscale
The above compound anticipates Formula (I) of the instant claims when Y = C(O); Z = absent; and X = heteroaryl.
Other combinations of Y-Z-X may be anticipated by the compound.
Volkmann discloses a method of treating diseases (e.g., epilepsy, multiple sclerosis, movement disorders, neuropathic pain) with the disclosed compounds. (Id., pp.19, 44, 52).
(ii) Claims 1–4, 6, 30, 46, and 48 are rejected under 35 U.S.C. §§ 102(a)(1) and (a)(2) as being anticipated by WO 2019/211668 (“Bryson”).
Bryson discloses ganaxolone derivatives according to formulae (I) and (II):
PNG
media_image4.png
558
587
media_image4.png
Greyscale
(Bryson, pp.5–6).
The following compounds were indexed in the Registry database:
PNG
media_image5.png
254
553
media_image5.png
Greyscale
PNG
media_image6.png
304
413
media_image6.png
Greyscale
PNG
media_image7.png
330
534
media_image7.png
Greyscale
The above compounds anticipate Formula (I) of the instant claims when Y = C(O) and:
Z = alkylene and X = cycloalkyl [first compound];
Z = methylene and X = alkylenecycloalkyl [first compound];
Z = absent and X = alkyl [second and third compounds];
Z = methylene and X = alkyl [second and third compounds]; or
Z = alkylene and X = alkyl [second and third compounds].
Other combinations of Y-Z-X may be anticipated by the compounds.
Bryson discloses a method of treating diseases (e.g., epilepsy, multiple sclerosis, movement disorders, neuropathic pain) with the disclosed compounds. (Id., pp.6, 19, 37, 38).
(iii) Claims 1–4, 6, 30, 46, and 48 are rejected under 35 U.S.C. §§ 102(a)(1) and (a)(2) as being anticipated by WO 2021/174205 (“Xu”).
Xu discloses ganaxolone derivatives according to formula (I):
PNG
media_image8.png
314
505
media_image8.png
Greyscale
(Xu, pp.2–3).
Xu discloses numerous compounds and embodiments:
PNG
media_image9.png
286
549
media_image9.png
Greyscale
PNG
media_image10.png
365
570
media_image10.png
Greyscale
PNG
media_image11.png
365
570
media_image11.png
Greyscale
(Id., pp. 25–36).
The above compounds anticipate Formula (I) of the instant claims when
Y = C(O) and Z = -O- or -NR1-; and X = substituted alkyl;
Y = C(O); Z = -OR3; and R3 = alkyl, wherein the alkyl is substituted; or
Y = C(O) and Z =
PNG
media_image12.png
83
134
media_image12.png
Greyscale
; Z1 = absent and connected to Y; RB, RC = H; and X = alkyl.
Other combinations of Y-Z-X may be anticipated by the compounds.
Xu discloses a method of treating diseases (e.g., depression, epilepsy) with the disclosed compounds. (Id., pp.1, 54–55).
Allowable Subject Matter
Claims 8, 13, and 14 are allowed.
Claims 16, 18, 20, 22, 27, 33, 37, and 39 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
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 submit an Automated Interview Request: http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached on 571-270-7674.
The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.M.N./Patent Examiner, Art Unit 1623
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
Prosecution Insights