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
The amendments to the claims filed October 28, 2024, are acknowledged and entered. Claims 1-17 are pending.
Priority
This application is a 371 of PCT/CN2023/091223, filed April 27, 2023, which claims priority of CN202210467997.6, filed April 29, 2022, and claims priority of CN202210769471.3, filed July 1, 2022, and claims priority of CN202211530536.5, filed December 1, 2022.
Information Disclosure Statement
Acknowledgement is made of the Information Disclosure Statements filed on October 28, 2024 and October 6, 2025. All references have been considered 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 which applicant may become aware of in the specification.
Claims Objections
Claims 2-5 are objected to because of the following informalities:
Claims 2-5 depend from claim 1 and are objected to for having extraneous text. The final line of each claim recites the phrase “wherein the definitions of R1… are as described above ” which is regarded as extraneous because the definitions of each of these variables carry over from claim 1. The extraneous phrase should be deleted.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 11-13 and 16-17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because the claims are drawn to a “use” and not to a patentable process, machine, manufacture, or composition of matter. The claims appear to claim a process; however, do not recite any steps involved in the process. “’Use’ claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101.” See MPEP 2173.05(q).
Claim Rejections - 35 USC § 112a
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 12-17 are is 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 method of treating a cerebrovascular or vascular disorder wherein the disorder is episodic migraine, migraine without aura, chronic migraine, pure menstrual migraine, menstrual related migraine, migraine with aura, migraine in children/adolescents, hemiplegic migraine, sporadic hemiplegic migraine, basal migraine, abdominal migraine, retinal migraine, cluster headache, dialysis headache, chronic headache of unknown cause, tension/pressure induced headache or allergy induced headache,
does not reasonably provide enablement for
Treating the full scope of diseases or preventing any of the diseases embraced by claims.
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.
Applicant teaches that a compound of formula (I) is an inhibitor of CGRP (Table I at [963] of the specification). However, CGRP is not known to be associated with all diseases of the instant claims. Applicant’s disclosure is only enabling for the treatment of conditions which Applicant has demonstrated may be treated by the instant compound, and of conditions which the prior art is already aware may be treated by a compound with the disclosed activity and for which Applicant has written support. Case law is clear on this point. In an unpredictable art, such as drug therapy to treat disease, models may be used for enablement only if there is a reasonable correlation between the activity in question and the asserted utility. Given the guidance provided by Applicant, one skilled in the art would not be able to practice the full scope of the invention without undue experimentation.
In evaluating the enablement question, several factors are to be considered. Note In re Wands, 8 USPQ2d 1400 and Ex parte Forman, 230 USPQ 546. The factors include: 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, and 7) the quantity of experimentation needed. The determination that “undue experimentation” would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations.
The nature of the invention & breadth of claims:
Claim 1 is drawn to a compound of formula (I).
Claim 12-13 and 16-17 depend from claim 1 and recite use of the claimed compound in preventing and/or treating a cerebrovascular or vascular disorder. Claims 13 and 17 recite specific disorders.
Claims 14-15 depends from claim 1 and recites a method for preventing and/or treating a cerebrovascular or vascular disorder. Claim 15 recites specific disorders.
Prevention is not defined in the specification. Merriam-Webster dictionary defines prevention as to keep from happening or existing. In view of this definition, prevention of disease as claimed would be understood to mean the disease is kept from occurring or existing.
The specification does not provide a complete definition of diseases embraced by the claims.
The nature of the invention is a method of treating and/or preventing a cerebrovascular or vascular disorder comprising administration of an inhibitor of CGRP (formula (I)). Because no definition of diseases embraced by the claims is provided, the scope of the claim is very broad.
The state of the prior art
The American Migraine Foundation (2016, CGRP Targeted Therapy for Migraine) teaches compounds that block the activity of CGRP may have use in the treatment of migraine and headache (page 1, What Are CGRP Blocking Medications?).
The state of the prior art otherwise is not aware that a compound which blocks the activity of CGRP treats or prevents the full scope of conditions embraced by the claims.
The Level of One of Ordinary Skill
The level of skill in the art is high. The artisan using the claimed invention would be a person with medical training such as a medical doctor or physician with an MD degree or the equivalent.
Predictability 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. Pharmacological activity in general is a very unpredictable area. Note that 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).
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.
Amount of guidance/working examples
Applicant provides in vitro data to show that a compound of formula (I) inhibits CGRP (Table I at [963] of the specification) thus suggesting the compound may have use in the treatment of migraines or headaches.
However, no experimental or other data is provided to show the instant compounds may have use in the treatment of the full scope of diseases claimed, and least of all those conditions for which there is no known association with CGRP. The specification does not provide any guidance to one of ordinary skill in the art to extrapolate the in vitro data provided by Applicant to the treatment of the many different forms of disease included in the scope of the method.
As per “prevention” of a claimed condition, it is presumed “prevention” of the claimed disease would require a method of identifying those individuals who will develop the claimed diseases before they exhibit symptoms. There is no evidence of record that would guide the skilled clinician to identify those who have the potential of becoming afflicted. Nothing in the specification teaches how one skilled in the art identifies a subject who’s disease will be prevented.
The quantity of experimentation needed:
MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on theevidence 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 and one skilled in the art could not practice the full scope of the claimed invention without undue experimentation.
Claim Rejections - 35 USC § 112b
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 1-17 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. The claims are indefinite for the reasons that follow:
Regarding claim 1, the term "preferably" renders the claim indefinite at each occurrence (see definitions of R1, Ra, R2, R3, X and Y) because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. See MPEP § 2173.05(d). It is suggested the claim be amended to delete all occurrences of “preferably”.
Regarding claim 1, the term “derivative” renders the claim unclear because the structure of such a derivative has not been defined. A “derivative” of the invention could correspond to any structure. It is not clear from Applicant’s disclosure what derivatives of formula (I) are embraced by the claims. The definition provided at paragraph [398] does not limit the claimed derivative to any particular structure. It is suggested that the term be deleted.
Regarding claims 1-5, the term “general” renders the claims indefinite because “general” implies more that what has been recited in the claim (see e.g. claim 1, “general formula (I), claim 2 “general formula (II)”…). The claims should be amended to delete the word “general”.
Claims 2-17 depend from claim 1, do not cure all of the abovementioned deficiencies regarding “preferably” and “derivative”, and therefore are also indefinite. It is suggested “derivative” be deleted from all dependent claims.
Claims 11-13 and 16-17 are drawn to “uses” of the claimed compound. The claims appear to claim a process; however, do not recite any steps involved in the process. “Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.” See MPEP 2173.05(q).
Regarding claim 13, 15 and 17, the word "including" (see “including Crohn’s disease…) renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. See MPEP § 2173.05(d).
Regarding claims 2-5, the phrase "wherein definitions of R1... are as described above" is improper as to what above means and, because definitions in dependent claims carryover from the claim from which they depend making this language superfluous and confusing. The phrases “wherein the definitions of R1… are as described above ” should be deleted.
Allowable Subject Matter
Claim 1 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action.
Claims 2-10 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims, and if rewritten to overcome the abovementioned objections.
The following is a statement of reasons for the indication of allowable subject matter:
The closest reference to the instant claims is Bell et al. (US2013/0231358, cited by Applicant in IDS filed October 28, 2024). Bell teaches compounds of generic Formula (I) (see [0008]) including Example 3 ([0266]; pictured below for convenience). The difference between Bell and the instant claims is that the instant claims require a bicyclic ring system corresponding to
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. Bell does not teach the required claim limitation and there is no teaching which would have motivated one of ordinary skill in the art before the effective filing date of the instant application to modify Bell into the claimed invention with any reasonable expectation of success.
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Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEVIN MARTIN whose telephone number is (571)270-0917. The examiner can normally be reached Monday - Friday 8 am - 5 pm.
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August 18, 2026
/K.S.M./Examiner, Art Unit 1624
/BRUCK KIFLE/Primary Examiner, Art Unit 1624
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