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 of Claims
Claims 1-22 are pending in the instant application.
Election/Restriction
This action is in response to an election from a restriction requirement mailed July 7th, 2026. Applicant has elected with traverse Group I, Claims 1-18, and a species election of N-[4-(4-chlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a single species of a compound of formula I.
After further consideration, the examiner has withdrawn the requirement for restriction. To this end, pending Claims 1-22 are presently under examination.
Priority
Acknowledgement is made of Applicant’s claim for foreign priority based on the ESP202130653 application filed in Spain on July 9th, 2021.
Information Disclosure Statement
The Information Disclosure Statement received September 9th, 2024 has been fully considered by the examiner, except where marked with a strikethrough.
Specification
The 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 of the errors of which Applicant may become aware of in the specification.
Drawings
Acknowledgement is made of the drawings received September 9th, 2024. These drawings are acceptable.
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 1-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating neuroblastoma, does not reasonably provide enablement for treatment and/or prevention of any tauopathy and/or any TDP-43 disease. 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 and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a method for the treatment and/or prevention of tauopathies and/or TDP-43 diseases comprising administering a compound of formula (I) as recited at instant Claim 1.
Breadth of the invention:
The scope of the invention is very broad, as it is drawn to the treatment or prevention of any tauopathy or any TDP-43 disease. This includes not only an array of mutually exclusive, distinct diseases and conditions, but also covers diseases and disorders that are yet known, but later classified as a tauopathy or TDP-43 disease. Can Applicant simply “reach through” and obtain patent protection for the prevention and/or treatment of diseases that are not yet known, or diseases that are presently known, and later classified as a tauopathy or a TDP-43 disease?
State of the prior art:
With respect to the treatment and/or prevention of tauopathies, Duggal et. al. (“Neuroprotective Approach of Anti-Cancer Microtubule Stabilizers Against Tauopathy Associated Dementia: Current Status of Clinical and Preclinical Findings”, Journal of Alzheimer’s Disease Reports, 2019; hereinafter referred to as Duggal) represents the state of the prior art.
At Page 195, Second Column, Second Paragraph, regarding Alzheimer-type dementias, Duggal states, “Drugs available clinically are for symptomatic relief only. No intervention is currently available as a preventive therapy.”
The speculative nature of therapies addressing tauopathy-associated dementia is addressed by Duggal at the last paragraph of Page 205. Duggal states “As much as some open questions and provocations remain out in front, the data reviewed here are encouraging and demonstrate the potential of therapeutic efforts of tau-based strategies for the future treatment of tauopathies, including AD.” This underscores the fact that such treatments are speculative.
Taken together, prevention of tauopathies is not well known in the art, and treatment of tauopathies in the absence of direct evidence is speculative.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis 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 be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
Beginning at Page 21, evidence is provided supporting activity of the instantly claimed compounds in inhibiting TTBK1 and TTBK2. In terms of treatment, Examples 4 and 6 demonstrate treatment of neuroblastoma.
This limited demonstration showing treatment of neuroblastoma is insufficient to provide enabling disclosure for the breadth of tauopathy and TDP-43 diseases instantly claimed. In fact, the speculative nature of such treatment is acknowledged in the instant disclosure. At Page 25, Applicant states, “TTBK1 inhibitors … may be good drug candidates for the treatment of diseases of the central nervous system that cause hyperphosphorylation of tau and TDP-43 proteins. To that end, the inhibitors described in the present patent could be used for the treatment and/or prevention of pathologies such as Alzheimer’s disease, amyotrophic lateral sclerosis and frontotemporal dementia …” The phrases “may be good drug candidates” and “could be used for treatment” indicates such methods are speculative, and the instant disclosure would not lead a person having ordinary skill in the art to be able to practice the breadth of the method claimed with reasonable assurance of success.
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 USPQ 2d 1510, 1513 (Fed. Cir. 1993).”
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. As alluded to above, a person having ordinary skill in the art would need to identify and/or develop metrics by which to ascertain which diseases or conditions beyond neuroblastoma are suitable for treatment by the instant method, with no assurance of success.
Genentech Inc. v Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for 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 and In re Fisher (CCPA 190) discussed above, to practice the claimed invention herein, a person having ordinary skill in the art would have to engage in undue experimentation to determine the suitability of treatment by practicing the instantly claimed method, with no assurance of success.
Claims 1-15, 17-19, and 21-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a compound of formula (I), stereoisomers thereof, or pharmaceutically acceptable salts thereof, and methods comprising the administration thereof, does not reasonably provide enablement for any of the isomers of a compound of formula (I). 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 and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to compounds of formula (I), any isomer thereof, pharmaceutically acceptable salts thereof, and methods comprising administration thereof.
Breadth of the invention:
The scope of the claimed invention is broad. The broadest reasonable interpretation of “any of the isomers thereof” extends to constitutional isomers. A person having ordinary skill in the art would readily envisage an array of constitutional isomers reading on the formula of a compound of formula (I) that are structurally distinct, and not necessarily operable within the context of the instantly claimed methods.
State of the prior 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 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.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis 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 be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
The compound core is depicted with specific substituents representing a narrow subgenus for which applicant has provided sufficient guidance to make and use; however, the disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. Applicant has not sufficiently disclosed examples enabling the breadth of the recitation of “any of the isomers” of a compound of formula (I), as this includes a myriad of compositional isomers that applicant has not described how to make and use in the instant disclosure.
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support the claims identifying the compound by such composition or formula. See MPEP 608.01(p).
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 that Applicant is not enabled for the breadth of isomers instantly claimed.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 16 and 20 are 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.
Claims 16 and 20 recite the compound, “N-[4-(2.4-chlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine”. At Page 16 of the specification, the following structure is provided:
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Conventional nomenclature of this compound would be N-[4-(2,4-dichlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine. Appropriate clarification is required.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 21 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 21 is drawn to a compound of formula (I) “for use thereof as a medicinal product.” This fails to introduce a further limitation on Claim 19, from which it depends, as this is a statement of intended use and does not provide a further limitation on the structure of the compound claimed. Statements of intended use are not given patentable weight. Per MPEP 2111.02, II., “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020)”.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
Claims 1-22 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.J.B./Examiner, Art Unit 1624
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
