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 .
DETAILED ACTION
Request for Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/27/2025 has been entered.
Status of 17/915,817
Claims 1, 5-7, and 16-20 are currently pending.
Priority
Instant application 17/915,817, filed 9/29/2022, claims priority as follows:
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Upon submission of the translated priority documents with the reply filed 6/30/2025, claims 1, 5-7, and 16-20 are granted the effective filing date of 12/16/2020.
Information Disclosure Statement
All references from the IDS submitted on 9/29/2022 have been considered unless marked with a strikethrough.
Objection to Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because Figures 1-4 are not able to be interpreted as they are pixelated and illegible. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Response to Arguments/Amendments
The amendment filed 10/27/2025 has been entered. Applicant has amended claims 1 and 5-7. No claims have been cancelled or added.
In the Final dated 7/31/2025, claims 1 and 5 were rejected under 35 U.S.C. 103. In response, Applicant has amended claims 1 and 5 to narrow the genus of formula I, and has argued that one of ordinary skill would not be directed to the compounds of the instant claims based on the reference Shanghai. Specifically, Applicant has narrowed the variable of Ar to a phenyl with a 3,5-bis(trifluoromethyl), 3-fluoro-5-trifluoromethyl, or 3,5-dimethoxy substitution pattern, and the linker variable to an alkyl chain with 4-7 carbons connected to a piperazine. Even though the genus of Shanghai suggests compounds of the instant claims, examples of Shanghai do not contain an alkyl linker longer than two carbons and do not have a heterocyclic group having more than one N atom in 84 compounds. A skilled artisan would need to pick and choose from a number of variables to arrive at the claimed compounds, none of which are directed to by the examples in of Shanghai.
Additionally, compounds of the instant claims have unexpected technical effects and are demonstrated to have the improved property of superior inhibitory activity of fibroblast growth factor receptors. These amendments and arguments overcome the rejection, which is therefore withdrawn.
Election/Restriction
Applicant’s election of Group I, claims 1-5, drawn to compounds of Formula I, without traverse in the reply filed 3/10/2025 is acknowledged. Applicant’s election of compound 10:
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in the reply filed 3/10/2025, without traverse, is also acknowledged.
Examination will begin with the elected species. In accordance with MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non- elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
In the Non-Final dated 4/1/2025, the elected species was searched and prior art was identified. During the initial search, an additional 102 rejection was identified and the scope was expanded to compounds of Formula (I), where the linker is a C1-C7 alkyl chain with piperidine or piperazine and R is H. Both 102 rejections have been overcome by Applicants arguments and amendments filed 6/30/2025. Subsequent examination in the Final dated 7/31/2025 was based on the species expansion to where the linker is C2-C7 alkyl chain with an azetidine, pyrrolidine, piperidine, or piperazine, where a 103 rejection was identified. In response, Applicant has overcome the rejection with the amendments and arguments filed 10/27/2025.
Claims 1 and 5 are allowable. Claims 6-7 and 16-20, previously withdrawn from consideration as a result of a restriction requirement, require all the limitations of an allowable claim. Pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement between inventions Group I, Group II, and Group III, as set forth in the Office action mailed on 2/3/2025 is hereby withdrawn and claims 6-7 and 16-20 are hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim Objections
Claims 6 and 7 are objected to because they contain pixelated images. Appropriate correction is required.
Claim Rejections - 35 USC § 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.
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 17-20 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.
Claim 17 recites, “comprises compound 10 or compound 36”, in reference to the anti-cancer drug administered to a patient. Claim 17 depends from claim 16, which ultimately depends from claim 1. Claims 1 and 16 do not contain a compound labeled “compound 10” or “compound 36”, and thus a lack of antecedent basis exists. Dependent claims 18-20 do not resolve the issue and are also rejected. Appropriate correction is required.
Claim 18 recites, “the dose is calculated according to a dosage of the compound 10 or the compound 36”, in reference to the administered dose to a patient in a method of treating cancer. The difference between a dose and dosage is unclear, and thus the limitation is indefinite. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 16-20 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 claims contain 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 use the invention commensurate in scope with these claims.
The instant specification, while being enabled for FGFR inhibition and non-small cell lung, stomach, and hepatic cancer cell line inhibition, does not reasonably provide enablement for treating all other cancers. 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.
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, of claim 1, and compounds recited in claim 5. The compounds are disclosed as inhibitors of FGFR to treat all cancers.
Breadth of the Claims
The claims are broadly directed to the use of compounds of formula I for the treatment of all cancers. The genus of cancers is not explicitly disclosed in the instant application, but one of ordinary skill would reasonably understand that the scope of all cancers is broad. The preferred embodiments of the instant disclosure include NCI-H1581 and SNU-16 cell lines (paras [0025] and [0027]), which are a non-small cell lung cancer and stomach cancer, respectively.
Level of Ordinary Skill in the Art
The artisans using Applicant’s method would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience.
The level of skill in the art is high; however, due to the unpredictability in the pharmaceutical arts, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro or in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
For example, different types of cancers affect different organs and have different methods of growth and/or harm to the body, and different vulnerabilities. The skill thus depends on the cancers. There are some cancers where the skill level is high and there are multiple successful therapeutic treatments. The mechanism of action in these situations, however, is not necessarily the same as is alleged for these compounds.
State of the Prior Art and Predictability in the Art
At the time of filing, there were multiple compounds targeting FGFR in development, and a variety of scaffolds are present in literature that target FGFR in in vitro assays (Krook, M. A. et. al. British Journal of Cancer. 2021, 124, 880-892.) However, none have been shown to have a broad spectrum of treatment of all cancers, and even suggests deficient data for specific cancers including haematological cancers (page 889, Conclusions and Perspectives). Further, there are different types of treatments available for cancer, including surgery, chemotherapy, hormonal therapy, biological therapy, and radiation. Not every treatment option is effective for every patient, and for some patients, combinations of the above treatment options are necessary to manage their symptoms. Therefore, the ability to treat cancer is unpredictable, much less the ability to anticipate which patients are at risk for the disease.
For example, the reference Krook, same as above, was identified as close prior art at the time of filing. Krook reviews FGFR mutations, therapeutic targets, and mechanisms of resistance (abstract), and specifically teaches small molecules erdafitinib, infigratinib, pemigatinib, and rogaratinib as able to treat urothelial cancer (page 886, “FGFR inhibitors in the treatment of urothelial cancers”), and pemigatinib, infigratinib, derazantinib, erdafitinib, and futibatinib as able to treat cholangiocarcinoma (page 887, “FGFR inhibitors in the treatment of cholangiocarcinoma”). Additionally, at the time of filing, erdafitinib was approved by the FDA to treat urothelial carcinoma (page 886, “FGFR inhibitors in the treatment of urothelial cancers”) and pemigatinib was the only FDA-approved FGFR inhibitor for the treatment of intrahepatic cholangiocarcinoma (page 887, “FGFR inhibitors in the treatment of cholangiocarcinoma”). Though evidence of treating urothelial carcinoma and cholangiocarcinoma with small molecules is provided by Krook, no other evidence of FGFR inhibitors treating all cancers was provided.
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).
Furthermore, there is no evidence of record, which would enable the skilled artisan in the identification of the people who have the potential of becoming afflicted with the numerous cancers claimed herein. That a single compound or class of compounds can be used to treat all cancers embraced by the claims is an incredible finding for which Applicant has not provided supporting evidence. Applicant has not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use for treating any or all cancers by administering the instant claimed compounds.
Amount of Direction Provided and Working Examples The only direction or guidance present in the instant specification is the small number of examples and preferred embodiments of non-small cell lung cancer and stomach cancer cell lines Applicant considers as treatable by the claimed compounds. The specification does not show any examples where compounds of the claims were used to treat the full scope of cancer as set forth in the claims, but merely demonstrates that certain compounds inhibit FGFR and treat non-small cell lung, stomach, and hepatic cancer. (See MPEP § 2164.02 (“Compliance with enablement requirement of 35 USC 112, first paragraph, does not turn on whether an example is disclosed… Lack of a working example, however is a factor to be considered, especially in a case involving an unpredictable and undeveloped art”.)
Quantity of Experimentation Needed to Make or Use the Invention Based on the Content of the Disclosure
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine what cancers out of all cancers would be treated and would furthermore then have to determine which of the claimed compounds in the instant invention would provide treatment of the claimed cancers.
A person having ordinary skill in the art at the time the invention was made would be faced with an undue amount of experimentation to use the compounds for the full scope of the claimed intended uses.
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.
The specification fails to provide enough support of the broad use of the methods of administering compounds of the claims in the treatment of cancers, and result in the necessitation of one of skill to perform an exhaustive search for which diseases can be treated by what compounds of the invention to practice the claimed invention.
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 an 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 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be treated by the compounds encompassed in the instant claims, with no assurance of success.
Conclusion
Claims 1 and 5 are allowed. Claims 6 and 7 are objected to. Claims 16-20 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kendall Heitmeier whose telephone number is (703)756-1555. The examiner can normally be reached Monday-Friday 8:30AM-5:00PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached on 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621