NON-FINAL REJECTION
Receipt is acknowledged of Applicants' Amendments and Remarks, filed Mar. 12, 2026.
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The rejections and/or objections set forth below are either maintained or newly applied, and constitute the complete set presently applied to the instant claims.
STATUS OF THE CLAIMS
Claims 3-6 and 10-11 have been canceled.
Claims 1, 2, 7-9, 12-16, 19, and 26 have been amended and incorporate no new matter.
No new claims have been added.
Thus, claims 1, 2, 7-9, and 12-26 now represent all claims currently pending and under consideration.
INFORMATION DISCLOSURE STATEMENT
No new Information Disclosure Statements (IDS) have been submitted.
RESPONSE TO ARGUMENTS
Applicant’s amendments and arguments filed Mar. 12, 2026, with respect to the rejections under 35 U.S.C. § 112 and 35 U.S.C. § 103 have been fully considered and are persuasive. Therefore, the rejections have been withdrawn.
However, upon further consideration, new grounds of rejection are set forth below.
NEW REJECTIONS
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
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, 13, and 19-26 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 methods of treating cancer, does not reasonably provide enablement for methods of preventing cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with the claims.
MPEP § 2164.01(a), citing In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), sets out the factors to consider whether experimentation is undue, which are addressed below.
(A) The breadth of the claims. The specification defines the term "prevention" to encompass "complete or nearly complete prevention of a disease or condition, for example when the patient or subject is susceptible to or at risk for a disease or condition; prevention can also include inhibition, i.e. stopping the development of pathologies" (para. [0069]). This definition includes steps taken prior to the development of a condition which precludes its coming into existence, which cannot be predicted or measured with any certainty.
In contrast, the term "treatment" is defined to encompass "1) suppression of the disease; for example, the inhibition of the pathology or symptoms of a disease, pathology, or condition of an individual who is experiencing or exhibiting a disease, pathology, or condition (i.e., preventing further development of pathology and/or symptomatology); or 2) improvement of the disease; for example, the improvement of the pathology or symptoms of the disease, pathology, or condition of an individual who is experiencing or exhibiting a disease, pathology, or condition (i.e., reversal pathology and/or symptomatology)" (para. [0070]).
Thus, "treatment" is limited to administering the claimed compounds to a subject after a disease has developed, while "prevention" encompasses administering the claimed compounds to a subject prior to the development of disease.
(B) The nature of the invention. The claims are broadly drawn to methods of preventing and/or treating a disease at least partially mediated by FGFR4 by administering a prophylactically and/or therapeutically effective amount of the claimed compounds to a patient in need thereof, wherein the disease is limited to specific cancers:
hepatocellular carcinoma, bladder cancer, breast cancer, cervical cancer, colorectal cancer, endometrial cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, esophageal cancer, gallbladder cancer, pancreatic cancer, thyroid cancer, skin cancer, leukemia, multiple myeloma, chronic lymphocytic lymphoma, adult T-cell leukemia, B-cell lymphoma, acute myeloid leukemia, Hodgkin or non-Hodgkin's lymphoma, Waldenstrom macroglobulinemia, hairy cell lymphoma, Burket lymphoma, melanoma, mesothelioma, neuroblastoma, testicular cancer, squamous cell carcinoma, glioblastoma, and rhabdomyosarcoma.
The specification provides working examples wherein compounds of formula (I) are shown to selectively inhibit FGFR4, and to inhibit the proliferation of human hepatoma Hep3B cells. However, the specification provides no examples of administering the claimed compounds to a subject prior to the development of a cancer.
(C) The level of predictability in the art. "Prevention" connotes the absolute absence of a condition which cannot reasonably be achieved with regard to the claimed conditions, or in medicine generally. In addition, there is no definitive method by which to determine whether a patient will develop the claimed conditions in the future, and thus, to be "a patient in need thereof." Even if a patient can be identified as having known risk factors for a disease, there is no way to predict that a patient will, in fact, later develop that disease. Further, the failure of a condition to develop cannot reliably be attributed to the active agent; the condition may reverse or resolve due to other factors. Thus, the terms "preventing” and "prophylactically effective amount" are unsupported by the disclosure.
(D) The amount of direction provided by the inventor. The specification discloses in vitro IC50 values for several of the claimed compounds against FGFR1 and FGFR4, which demonstrate their potency and selectivity for FGFR4 (Table 1); as well as IC50 values against Hep3B hepatoma cells, which demonstrate their ability to inhibit cancer cell proliferation. However, no specific embodiments or working examples in which the claimed cancers are prevented, or their development stopped, are disclosed or tested.
(E) The quantity of experimentation needed to make or use the invention. Because "preventing" a disease by the prior administration of an active agent cannot be objectively predicted, measured, or achieved with any certainty, coupled with a lack of guidance and direction provided by the instant disclosure, a skilled artisan could not practice the invention commensurate with the scope of the claims without undue experimentation.
This rejection can be overcome by amending the claims to omit the terms "preventing" and "prophylactically."
Claim Objections
Claims 17, 18, 24, and 25 are objected to under 37 CFR 1.75 as being a substantial duplicate of claims 9, 16, 22, and 23, respectively. Specifically:
The scope of claim 17 is identical to that of claim 9.
The scope of claim 18 is identical to that of claim 16.
The scope of claim 24 is identical to that of claim 22.
The scope of claim 25 is identical to that of claim 23.
When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). This objection can be overcome by canceling claims 17, 18, 24, and 25.
Claims 12, 13, and 19-26 are objected to because of the following informalities: the claims recite administering a "therapeutically amount" of the claimed compounds. This appears to be a typographical error which should be amended to a "therapeutically effective amount."
Appropriate correction is required.
Allowable Subject Matter
Claims 1, 2, 7-9, and 14-16 are allowed.
The following is a statement of reasons for the indication of allowable subject matter:
The closest prior art is Li et al. (CN 107286130A, of record), which discloses compounds of formula (I), shown below for comparison with claimed formula (I):
Claimed Formula (I)
Li et al. Formula (I)
PNG
media_image1.png
196
354
media_image1.png
Greyscale
PNG
media_image2.png
236
430
media_image2.png
Greyscale
X3 of formula (I) of Li et al. corresponds to Z of the instantly claimed formula (I).
Claim 1 defines Z as C(R6)2, wherein both R6 moieties and the carbon atom connected thereto together form C3-8 cycloalkyl. In contrast, Li et al. define X3 as carbon or nitrogen, but is silent as to any substitution at X3. Therefore, Li et al. provide no teaching, suggestion, or motivation to arrive at compounds falling within the scope of the instant claims.
CONCLUSION
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 10:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARA E. TOWNSLEY/Examiner, Art Unit 1629
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