DETAILED ACTION
This office action is in response to the Applicant’s filing dated March 13th, 2026.
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 .
Priority
This application is a 371 of PCT/US2022/030230 filed on May 20th, 2022; and has a PRO of 63/191,636 filed on May 21st, 2021.
Status of Claims
Claims 67-90 are pending in the instant application. Acknowledgement is made of Applicant’s remarks and amendments filed on March 13th, 2026.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on March 13th, 2026 is acknowledged.
Claims 85-90 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 13th, 2026.
Applicant’s species election without traverse of Example 4 shown below in the reply filed on March 13th, 2026 is acknowledged:
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A prior art search was conducted for the elected species.
No prior art was found.
Search was expanded to include the full scope of compounds of Formula (I).
No prior art was found.
Claims 67-84 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 85-90, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on January 16th, 2026 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, 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 Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable.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 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 85-89 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 inhibiting AXL in vitro with a compound of Formula (I) on pages 114-117 in Table 1, does not reasonably provide enablement for treating all diseases, conditions or disorders associated with AXL, including 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 use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention and breadth of the claims
The invention relates to a method of treating a subject having or susceptible to a disease, condition or disorder associated with AXL, including cancer.
Claims 85-89 are directed to a method of treating a subject having or susceptible to a disease, condition or disorder associated with AXL, including cancer; comprising administering a compound of Formula (I). Thus, the claims are extremely broad with regards to the diseases to be treated as well as the possible compounds that can be utilized.
2. The state and predictability of the art, and relative skill of those in the art
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain).
As illustrative of the state of the art, the examiner cites Gura et al (Science, New Series, (1997), 278(5340), 1041-1042), cited for evidentiary purposes, teaches that researchers face the problem of sifting through potential anticancer agents to find ones promising enough to justify human clinical trials. The reference further teaches that, since formal screening began in 1955, many thousands of drugs have shown activity in cell or animal models, but only 39 have actually been useful for chemotherapy (page 1041, first and second paragraphs). With regard to unpredictability, Johnson et al (British Journal of Cancer, (2001), 84(10), 1424-1431), also cited for evidentiary purposes, teaches that the in vivo activity of 39 different agents in a particular histology in a tumor model did not correlate with activity in the same human cancer (page 1426, Results). Myers et al (Journal of Medicinal Chemistry, (2016), 59(8), 3593-3608), also cited for evidentiary purposes, teaches that clinically useful AXL inhibitors can be unpredictable in cancer therapy due to their selectivity profiles, citing that many AXL inhibitors are pan kinase inhibitors, which can result in the inhibition of kinases that are essential for physiological functions, and consequently result in severe side effects. AXL inhibitors are rarely be employed in the clinic on their own, and drug combinations usually lead to incremental adverse effects (page 3603, left column, last paragraph; right column, first paragraph). Moreover, studies have shown that ablation of AXL signaling in mice favors a tumor promoting environment in the colon by increasing production of proinflammatory cytokines and reducing clearance of apoptotic neutrophils in the intestines (page 3603, right column, last paragraph).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability of the art” In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970).
Accordingly, the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statutory requirements. Furthermore, the mechanism of action of anticancer agents is often unknown or highly unpredictable, and the administration of such agents is frequently accompanied by undesirable side effects.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides data for inhibition of AXL with compounds of Formula (I) in vitro on pages 114-117 in Table 1, but it is not sufficient to provide support for the full scope of compounds encompassed by the claims or for the full scope of all diseases, conditions or disorders associated with AXL, including cancer.
The specification provides no particular direction or guidance for determining the particular administration regimens (e.g. timing, administration routes, etc) necessary to treat all diseases, conditions or disorders associated with AXL, including cancer, encompassed by the claims, particularly in humans. At best, an "effective amount" is exemplified as a dosage sufficient to provide treatment for AXL inhibition.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that any compound of Formula (I) could be predictably used as treatment for all conditions or disorders associated with inhibiting AXL, including cancer.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a 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" (42 USPQ 2d 1001, Fed. Circuit 1997). A review of the state of the art fails to reveal the mechanism of action or experimental data regarding the use of any compound of Formula (I) in the specification to treat any disease, condition or disorder related to AKL inhibition, including cancer. Determining if any particular claimed compound would treat any disease, condition or disorder associated with AXL inhibition, including cancer, would require synthesis of the compound, formulation into a suitable dosage form, and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. As noted in supra, even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the inventions of instant claims 85-89 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter:
In a search of the claimed compounds and composition comprising of Formula (I), and method of inhibiting the activity of AXL in a subject comprising administering a compound of Formula (I); the claimed compounds and composition comprising of Formula (I), and method of inhibiting the activity of AXL in a subject comprising administering a compound of Formula (I) were found free of prior art.
Conclusion
Claims 85-89 are rejected.
Claims 67-84 and 90 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER L JOHNSON whose telephone number is (571)272-1672. The examiner can normally be reached Monday - Friday 08:00AM - 5:00PM EST with Flex on Fridays.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.L.J./Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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