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
The present office action is in responsive to November 13, 2023 Information Disclosure Statement and corresponding miscellaneous documents.
Claims 1-20 are pending, claims 1-3, 12-15 and 19-20 are original, claims 4-11 and 16-18 are amended and claims 21-22 are cancelled in the above-identified application.
Priority
U.S. Pat. Appln. Ser. No.: 18/554,211, Filed: October 6, 2023 is a 371 Nat.’l Stage Entry of WO 2022/217248 A1 (i.e., PCT/US2022/071586, Intern.’l Filing Date: April 7, 2022; Intern.’l Pub. Date: October 13, 2022), which claims foreign priority to U.S. Prov. Appln. No. 63/173,369, Filed: April 10, 2021.
Information Disclosure Statement
An Information Disclosure Statement (IDS) submitted on November 13, 2023 is in compliance with the provisions of 37 CFR 1.97.
Accordingly, Information Disclosure Statements have been considered by the Examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conc lude 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 20 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
In particular, claim 20 lacks clarity and is vague, ambiguous and indefinite for recitation of the phrase "wherein the movement disorder is . . . damage or side effect from stroke", such that the metes and bounds or scope of the claimed invention is indeterminate. It is unclear what the term or phrase "damage" or ”a side effect” actually is measured, determined or defined in the context of a movement disorder, as a direct stroke symptom associated with physiological or neurological impairments or direct result based on subsequent physiological.
Moreover, claim 20 recites a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite, such that the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
Here, claim 20 recites the broad recitation Ataxia, and the claim also recites “(e.g., spinocererebellar ataxia)” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because, the recitation of a phrase within parentheses renders the claim indefinite and there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
To overcome this rejection, Applicants are encouraged to make appropriate clarifying claim amendments to specifically define what constitutes "damage" or "side effect" based on supported specific information, which may include clinical criteria and the like.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 1-20 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 claim(s) contains 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.
Claims 1-20 are rejected under 35 U.S.C. 112(a), because the specification, while being enabling for:
[I] compounds of Formula II(A) and Formula (IIB) shown below:
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OR
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with different and specific claim scope defined below:
[b] Formulas (IIA) and (IIB): where: X1 = C(R4A)(R4B)
[c] Formulas (IIA) and (IIB): where: X1 = N(R4C)
X1 is C(R4A)(R4B)
R1A and R1B :
each independently H, (C1-C4)alkyl; or
together with the carbon atom to which they are attached, form a spiro-(C3-C6)cycloalkyl; and
R2A, and R2B are each independently H or (C1-C4)alkyl,
R3A, R3B, R3C, and R3D each independently H, halogen,
(C1-C4)haloalkyl,-CN
R4A and R4B:
each independently are H or (C1-C4)alkyl; or
together with the carbon atom to which they are attached, form a (C3-C6)cycloalkyl;
proviso 1
provided that:
when R1A, R1B, R2A, R2B, R3A, R3B, R3C, and R3D are each hydrogen,
then:
(i) at least one of R4A and R4B is a group other than hydrogen.
X1 = N(R4C)
R4C is H or (C1-C4)alkyl;
R1A and R1B each independently H or (C1-C4)alkyl (CF3);
R2A, and R2B are each independently H or (C1-C4)alkyl;
R3B = halogen (i.e. F) or (C1-C4)haloalkyl (CF3);
R3A, R3C, and R3D each independently H
proviso 2
provided that:
when R1A, R1B, R2A, R2B, R3A, R3B, R3C, and R3D are each hydrogen,
then:
(ii) R4C is a group other than hydrogen; and
when X1 is N(R4C) and only one of R1A, R1B, R2A, R2B, R3A, R3B, R3C, R3D, and R4C is a group other than hydrogen,
then
(i) R1A is not methyl;
(ii) R1B is not methyl; and
(iii) R3C is not methoxy or ethoxy.
Examples 1 to 60, i.e., X1 = C(R4A)(R4B) + provisos
Examples 65 to 74; i.e., X1 = N(R4C) + provisos
[II] Specific Compounds (corresponds to chart above)
[b] Example compounds 1-60 or a pharmaceutically acceptable salt thereof:
where X1 = C(R4A)(R4B) + proviso 1, corresponding intermediates and methods for making intermediates thereof;
[c] Example compounds 65-74 or a pharmaceutically acceptable salt thereof:
where X1 = N(R4C)+ proviso 2, corresponding intermediates and methods for making intermediates thereof; and
[III] methods of treating essential or resting tremor (i.e., not considered a model for Parkinson's disease (PD) resting tremor) or suppressing tremor activity (as exemplified by assay examples),
DOES NOT reasonably provide enablement or sufficient guidance for:
Broad scope of ANY or ALL:
compounds of Formula (Id) or (If) or pharmaceutically acceptable salt, hydrates or solvates thereof; corresponding to:
ANY or ALL pharmaceutical compositions thereof, comprised of:
a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof; and
a therapeutically effective amount of ANY or ALL or one or more other therapeutic agents (i.e., as in claim 17).
A method of treating ANY or ALL neurological or psychiatric disease(s) or disorder(s) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof (i.e., as in claim 18).
where
ANY or ALL neurological or psychiatric disease(s) or disorder(s) is ANY or ALL movement disorder(s) (i.e., as in claim 19).
ANY or ALL movement disorder(s) selected from:
Tremor; Dyskinesia; Dystonia; Tics; Dysphonia; Ataxia (e.g., spinocerebellar ataxia); Myoclonus; Essential Tremor; Epilepsy; Tardive Dyskinesia; Restless Leg Syndrome; Tourette Syndrome; Multiple System Atrophy (MSA); Multiple Sclerosis; Huntington's Disease; Parkinson's Disease; Parkinsonism; Parkinson's disease tremor, Atypical Parkinsonisms; Wilson's Disease; or
ANY or ALL damage or side effect(s) from Stroke (i.e., as in claim 20).
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
These factors include the following:
1. Scope Of The Claims.
The scope of the claims relates to these classes exemplified by independent claim types:
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or psychiatric diseases or disorders.
Thus, the scope of claims is very broad.
Nature Of The Invention.
The nature of the invention relates to:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
3 & 4) State of the Art and Predictability In The Art.
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally
considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (i.e., see MPEP 2164.03)
Amount Of Guidance Provided By Applicants and 6. Working Examples.
Applicants provide guidance in the detailed specification supported by:
Working examples exemplified by:
Compounds of Formula (I) or pharmaceutically acceptable salts thereof:
Examples 1 to 60 (i.e., where X1 = C(R4A)(R4B))
Example 65-74 (i.e., where X1 = N(R4C)), respectively,
supported by synthetic preparative examples of intermediates and final products (i.e., including characterizing data, which may be adapted or modified by a skilled artisan to make other compounds encompassed by the present invention);
Other than that which described supra in this rejection, there is NO teaching in the specification directed to any other examples encompassing the:
Broad scope of claimed compounds encompassed by all generic formulas defined therein, and/or
Also, a lack of enablement arises when a patent specification fails to provide adequate guidance or sufficient examples to cover the full scope of a genus of compounds; i.e., e.g.,
particularly even with a direct bioisosteric substitution (i.e., e.g., X1 = C(R4A)(R4B) instead of X1 = N(R4C) would not predictably result in derivatives substituted with identical moiety substitutions on chromene/chromane core due to unpredictable synthetic or bioelectronic unfeasibility or instability without empirical evidence (working examples) in the specification.
Compounds
[b] Formulas (IIA) and (IIB): where: X1 = C(R4A)(R4B)
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[c] Formulas (IIA) and (IIB): where: X1 = N(R4C)
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Assays: Biological Data Directed Only To Tremors or Induced Tremors
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While conventional biological assays are directed to:
“A method for treatment of essential tremor or tremor suppressing activity in a subject in need of such treatment, which comprises administering a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof (i.e., as in claim 20)”; i.e., and determine/identify efficacy/testing of selected compounds of the claimed invention in art known in vivo rat assay models:
Harmaline-induced Tremor Model for Essential tremor (ET) symptoms; and/or
Tacrine or Cholinomimetic-induced tremulous jaw movements (TJMs) in rat assays, via known preclinical test that extensively used to validate via known and predictable correlation based on a pharmacological model of resting tremor (i.e., , not considered a model for Parkinson's disease (PD) resting tremor).
These rat model assays only show utility in treatment of specific tremors as there is:
NO teaching directed to broad scope of ANY or ALL neurological or psychiatric disorders, based on the insufficient examples in the specification (i.e., e.g., there is lack of target disease data, no identified specific disease indication,
NO basis for demonstrating any therapeutic effect or what compounds of the present invention adaptable for treatment of the general aforementioned disorders or diseases as a whole
Therefore, the instant application fails to satisfy the enablement requirement of 35 U.S.C. § 112(a) because the specification does not provide an adequate teaching for one of ordinary skill in the art to practice the full scope of the claimed invention without undue experimentation. Identified assays taught in the specification provide a mere starting point or "invitation to a research project" and does not establish a sufficient or reasonably predictable correlation to all claimed and identified diseases in claim 20:
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.A person skilled in the art would have to engage in substantial and undue experimentation (such as conducting extensive animal studies or clinical trials not described) to bridge the significant unpredictable gap between the disclosed in vivo rat activity and the claimed therapeutic effect in the full scope of subjects.
Regarding noted above, these cannot be simply willed into existence. As was stated in Morton International Inc. v. Cardinal Chemical Co., 28 USPQ2d 1190 “The specification purports to teach, with over fifty examples, the preparation of the claimed compounds with the required connectivity. However,...there is no evidence that such compounds exist...the examples of the '881 patent do not produce the postulated compounds...there is...no evidence that such compounds even exist.
The same circumstance appears to be true here. Hence, Applicants must show that the scope of claimed compounds and other requirements yields all the desired effects of scope claimed, other than those exemplified by the limited Experimental Example section of the present invention, where examples can be made/ used for the stated purpose in all situations across the board, not just in animals, but also in human subjects or limit the claims accordingly.
7. Level Of Skill In The Art (High)
An ordinary artisan in the area of drug development would have experience in screening chemical compounds for particular activities. Screening of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target, (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can often be employed, developing a therapeutic method, as claimed, is generally not well-known or routine, given the complexity of certain biological systems.
An ordinary artisan with expertise in the biological areas of molecular biology, immunology, biopharma, biotech, pharmacology, medicinal chemistry organic, biological, organic, and /or related drug development technologies would recognize the significance of biological mechanisms of action involving use of compounds of the present invention for treatment of neurological or psychiatric diseases as indicated by the specification.
The process of finding new drugs that have in vitro activity against a particular biological target, (i.e., receptor, enzyme, etc.) is well known.
Additionally, while high throughput screening assays can often be employed, developing a therapeutic method for a complex invention as claimed, is generally not well-known or routine, given the complexity of certain biological systems. Screening of new drug candidates, while complex, is routine in the art.
MPEP §2164.01 (a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)."
That conclusion is clearly justified here as Applicants are not enabled for making or using all these compounds (i.e., as described in general terms, inc., but not limited to starting materials, intermediates, etc.) or pharmaceutical compositions thereof (i.e., e.g., by using not specifically reagents and/or, reactions conditions, etc. ) or treating ALL diseases taught in the specification.
In summary, the instant application fails to satisfy the enablement requirement of 35 U.S.C. § 112(a) because the specification does not provide an adequate teaching for one of ordinary skill in the art to practice the full scope of the claimed invention without undue experimentation. The claimed invention is directed to a broad compound genus scope or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions (i.e., defined in claims 1-17) and treatment methods directed to all neurological or psychiatric disorders (i.e., as defined in claims 18-20), while the specification only teaches:
compounds directed to a limited subgenus of compounds of Formulas (IIA) and (IIB) as defined supra;
corresponding pharmaceutical compositions do not teach the additional element of “one or more other therapeutic agents”; and
data only supports methods for treating essential tremor or suppression of tremor activity
without resorting to undue experimentation; i.e., e.g.,:
the burden is on the applicant to show that the disclosure is enabling for the full scope of the claimed invention, but here, the disclosure of success based on suppression of tremor activity, without out indicating what other diseases to treat is not commensurate with the breadth of the claim.
Accordingly, above-identified claims of the instant invention are non-enabled under 35 U.S.C. § 112(a).
Citation of Relevant Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure. Prior Art Registry Compounds identified below are relevant non-substituted parent sulfonamide-chroman compounds from which compounds of the present invention are chemical derivatives.
[A] Registry RN 1280984-95-4
[B] Registry RN 1564707-59-0
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CONCLUSION
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to GRACE C HSU whose telephone number is (571) 270-1689.
The Examiner can normally be reached Monday-Friday 7:30 am - 6 pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, Applicants is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Jeffrey H. Murray can be reached on 571-272-9023.
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/G.C.H./
Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624