DETAILED ACTION
This office action is in response to the Applicant’s filing dated February 3rd, 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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 February 3rd, 2026 has been entered.
Priority
This application is a CON of 16/819,934 filed on March 16th, 2020; which is a CON of 16/163,829 filed on October 18th, 2018; which is a CON of 15/436,333 filed on February 17th, 2017; which has a PRO of 62/297,450 filed on February 19th, 2016.
Status of Claims
Claims 1, 4-8 and 10-20 are pending in the instant application. Acknowledgement is made of Applicant’s remarks and amendments filed on February 3rd, 2026. Acknowledgment is made of Applicant’s amendment of claim 1; and cancelation of claims 2-3.
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 1, 4-8 and 10-20 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 stabilizing p53 Y220C mutants with the compound from Example 2 (page 237, paragraph [0449]) in an in vitro HTRF assay as shown in Example 702 on pages 237-239 in the specification, it does not reasonably provide enablement for treating all p53 Y220C mutation related cancers with any compound claimed. 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 cancer that expresses a p53 mutant, wherein the p53 mutant is Y220C.
Claims 1, 4-8 and 10-20 are directed to a method of treating cancer that expresses a p53 mutant, wherein the p53 mutant is Y220C, comprising administering to a subject a therapeutically effective amount of a compound of the formula shown below:
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that binds the p53 mutant in the subject. The above formula permits the addition of heteroatoms producing different core scaffolds with different heteroatom counts, ring electronics, and geometries; permits changes in regiochemistry, rotating pharmacophore orientation and substituent topology; and further permits the combining aromatic, saturated, perfluoroalkyl, heteroatom-bearing, and hydrogen options that are not a recognized class and are not shown functionally equivalent. 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, cited for evidentiary purposes in a previous Office action, 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, also cited for evidentiary purposes in a previous Office action, 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). Pfister et al, also cited for evidentiary purposes in a previous Office action, teaches “Mechanistically, wild-type p53 binds DNA in a sequence-specific manner to mediate its functions, whereas mutant p53 fails to bind to a wild-type p53 consensus sequence” (page 2, left column, first paragraph). “One p53 mutant may be observed to behave differently than another p53 mutant based on changes in conformation, binding partners, cellular localization, and transactivation capability” (page 13, right column, last paragraph). “It must be emphasized that the mechanism of mutant p53-transcription factor and mutant p53-coactivator interaction is not well understood” (page 18, left column, last paragraph). “Hotspot p53 mutants affect transcription in ways that are currently unpredictable” (page 18, right column, first paragraph). It is well established in the prior art that the functional behavior of genetic mutations in tumors is highly context-dependent; influenced not only by the specific mutation itself, but also by the tumor microenvironment and dominant signaling pathways. Pfister states, “As each tumor is unique in its development, it should be considered at this point that mutant p53 may be a promiscuous transcription factor that is used by the tumor cell–based on its specific mutations, dominant signaling pathways, and interaction with the microenvironment—in a manner that is selectively advantageous” (page 11; left column, last paragraph; right column, first paragraph). This suggests that even if a compound is known to bind to a p53 mutant, the functional effect of that interaction cannot be reliably predicted across all mutant contexts. The tumor specific microenvironment, signaling, mutation-specific conformational changes and interaction with other oncogenic drivers create a level of biological unpredictability.
While it is noted that FRET drug targeting efficacy monitoring is known in the art as evidenced by Nobis et al, cited for evidentiary purposes in a previous Office action, who teaches fluorescence resonance energy transfer (FRET) used to monitor drug-targeting efficacy in a transgenic p53-mutant model of pancreatic cancer (page 4674, Abstract paragraph, lines 4-7), further teaching that FRET is a valuable preclinical tool to assess drug delivery and efficacy in live tumors (page 4675, left column, last paragraph); it is not particularly relevant (or given patentable distinction) to the claimed invention of treating cancer that expresses a p53 mutant, wherein the p53 mutant is Y220C, comprising administering to a subject a therapeutically effective amount of a claimed compound, because increasing the ability of the p53 mutant (bound by a claimed compound) to bind DNA by at least about 50% is a function of stabilization that is inherent to the compound.
“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 stabilizing p53 Y220C mutants with the compound from Example 2 (page 237, paragraph [0449]) in an in vitro HTRF assay as shown in Example 702 on pages 237-239 in the specification, but it is not sufficient to provide support for the full scope of treating all cancers associated with p53 Y220C mutations, with any claimed compound.
The specification provides no particular direction or guidance for determining the particular administration regimens (e.g. timing, administration routes, etc) necessary to treat all p53 Y220C mutation cancers encompassed by the claims, particularly in humans. At best, an "effective amount" is exemplified as a dosage sufficient to provide treatment for p53 Y220C mutation cancer. While experimentation is presented for stabilizing p53 Y220C mutants with the compound from Example 2 in an in vitro HTRF assay as shown in Example 702 on pages 237-239 in the specification, there is no experimentation or mechanism or action presented or discussed in the specification regarding the treatment of all p53 Y220C mutation cancers.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed in supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that any compound listed in the specification could be predictably used as treatment for all conditions or disorders associated with p53 Y220C mutant 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 compounds in the specification to treat any p53 Y220C mutant cancer. Determining if any particular claimed compound would treat a conditions or disorders associated with p53 Y220C mutant 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 1, 4-8 and 10-20 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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4-8 and 13-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-6, 14-15, 17-18, 24-26, 29, 33, 35-37 and 40 of copending Application No. 17/348,488 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference application are drawn to a method of treating cancer comprising administering an effective amount of a compound of the formula shown below:
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which is nearly identical to the instantly claimed formula. The claims of the reference application state that variable A can be an unsubstituted alkynylene (explicitly claimed in dependent claims 17-18 of the reference application), which would ultimately make the reference formula identical to the instantly claimed formula. The remaining variables of the reference application overlap with the instant application, meaning the same compounds are being administered to treat the same disease (cancer), in the same subjects (subjects with cancer, with a p53 mutation at Y220C).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 4-8 and 10-20 are rejected.
No claim is 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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/C.L.J./Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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