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 and Response to Amendments
The amendments filed May 26, 2026 have been acknowledged and entered. Claims 1, 3-6, 8-15, 17-18, 20, 23, 26 and 29 are pending.
Information Disclosure Statements
Acknowledgement is made of the Information Disclosure Statement filed on May 26, 2026 . All references have been considered except where marked with a strikethrough.
Election/Restriction
The present examination is based on Applicant’s election of Group 1 (presently claims 1, 3-5, 15 and 17-18) in the response filed December 2, 2025. Applicant amendments have overcome all previous art rejections.
Claims 1, 3-5, 15 and 17-18 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 6, 8-14, 20, 23, 26 and 29 directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on October 7, 2025 is hereby withdrawn.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 Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable.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 Objections
Claim 18 is objected to because of the following informalities:
Claim 18 is objected to for not explicitly defining the variables R1, R2…A, X, Y, and L. It is noted that that claim defines the variables by reference to claim 1; however, claim 18 is an independent claim and therefore it is suggested the claim be amended to explicitly define the variables in the body of the claim.
Appropriate correction is required.
Withdrawn Rejections
Applicant is notified that any outstanding rejection or objection that is not expressly maintained in this Office Action has been withdrawn or rendered moot in view of Applicant’s amendments and/or
remarks.
Rejections Necessitated by Applicant Amendment
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 8-14 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 a method of treating a lymphoma, a cervical tumor, a lung tumor, a colon tumor and/or metastases thereof comprising administration of a compound of formula (I) to a subject, does not reasonably provide enablement for
A general method of treating or preventing a hyperproliferative disease and/or disorder responsive to induction of cell death in a subject, including prevention of a lymphoma, a cervical tumor, a lung tumor, a colon tumor and/or metastases thereof
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 Casein kinase 1 alpha and/or Casein kinase 1 delta (page 3, summary of invention) and has activity against Bub1 kinase (page 331), EGFR (page 330). Applicant additionally demonstrates that compounds of the invention may have use in the treatment of lymphoma, colon cancer and lung cancer (see Proliferation Assays beginning at page 334). However, these activities are not known to be correlated with the treatment of the entire scope of diseases claimed which is incredibly broad. 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 8 depends from claim 1 and recites a method of treating or preventing a hyperproliferative disease and/or a disorder responsive to induction of cell death in a subject, comprising administering a compound of general formula (I) according to claim 1 to the subject.
Claim 9 depends from claim 8 and recites wherein the hyperproliferative disease and/or disorder responsive to induction of cell death is a haematological tumour, solid tumour and/or metastases thereof.
Claims 10-14 depend directly or indirectly from claim 9 and include the limitation “prevention”
The specification teaches “subject” includes humans (page 63, lines 20-27).
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 hyperproliferative diseases embraced by the claims. Nor does the specification provide a definition of disorders that are responsive to induction of cell death.
The nature of the invention is a method of treating or preventing disease with a compound having the activity of formula (I). Because no complete definition of hyperproliferative diseases or disorders responsive to induction of cell death is provided, the method is very broad including at least a general method of treating all cancers known in the art.
The state of the prior art
No compound has ever been found to treat cancers of all types generally. Since this assertion is contrary to what is known in medicine, proof must be provided that this revolutionary assertion has merits. The existence of such a “silver bullet” is contrary to our present understanding of oncology. The state of the art is not indicative any pharmaceutical agents that are useful in the treatment of cancer generally. Cecil Textbook of Medicine states that “each specific type has unique biologic and clinical features that must be appreciated for proper diagnosis, treatment and study” (see the enclosed article, page 1004). Different types of cancers affect different organs and have different methods of growth and harm to the body. Also see In re Buting, 163 USPQ 689 (CCPA 1969), wherein 'evidence involving a single compound and two types of cancer, was held insufficient to establish the utility of the claims directed to disparate types of cancers'. Thus, it is beyond the skill of oncologists today to get an agent to be effective against cancers generally.
A similar statement appears at In re Application of Hozumi et al., 226 USPQ 353: “In spite of the vast expenditure of human and capital resources in recent years, no one drug has been found which is effective in treating all types of cancer. Cancer is not a simple disease, nor is it even a single disease, but a complex of a multitude of different entities, each behaving in a different way”. There are compounds that treat a modest range of cancers, but no one has ever been able to figure out how to get a compound to be effective against cancer generally, or even a majority of cancers.
The attempts to find compounds to treat the various cancers arguably constitute the single most massive enterprise in all of pharmacology. This has not resulted in finding any treatment for tumors generally. Indeed, the existence of such a "silver bullet" is contrary to our present understanding in oncology. This is because it is now understood that there is no “master switch” for cancers generally; cancers arise from a bewildering variety of differing mechanisms. Even the most broadly effective antitumor agents are only effective against a small fraction of the vast number of different cancers known. This is true in part because cancers arise from a wide variety of sources, primarily a wide variety of failures of the body's cell growth regulatory mechanisms, but also such external factors such as viruses (an estimated at least 20% are of viral origin e.g. Human papillomavirus, EBV, Hepatitis B and C, HHV-8, HTLV-1 and other retroviruses, and quite possibly Merkel cell polyomavirus, and there is some evidence that CMV is a causative agent in glioblastoma), exposure to chemicals such as tobacco tars, excess alcohol consumption (which causes hepatic cirrhosis, an important cause of HCC), ionizing radiation, and unknown environment factors.
Similarly, In re Novak, 134 USPQ 335, 337-338, says “unless one with ordinary skill in the art would accept those allegations as obviously valid and correct, it is proper for the examiner to ask for evidence which substantiates them.” There is no such evidence in this case for a compound that treats all types of cancer. Likewise, In re Cortright, 49 USPQ2d 1464, states: “Moreover, we have not been shown that one of ordinary skill would necessarily conclude from the information expressly disclosed by the written description that the active ingredient” does what the specification surmises that it does. That is exactly the case here. Moreover, even if applicants’ assertion that cancer in general could be treated with these compounds were plausible --- which it is not ---, that “plausible” would not suffice, as was stated in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297, 1301: “If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success.”
Recently, Wu (Journal of Hematology & Oncology 2022 (15) 143) discloses that between 1991 and 2021 there have been 228 new cancer drugs approved by the U.S. Food and Drug Administration of which 120 of these are drawn to the treatment of solid tumors alone (Abstract). Wu teaches that there are 21 different approved drugs for treating lung cancers, some of which have different cellular targets (Table 1, page 5). Similarly, breast cancer (see Table 2, page 10) has 22 different drugs that have varied cellular targets and are indicated for different types of breast cancer. More still, Table 4 (page 17) indicates that there are 17 different drugs available to treat different forms of gastrointestinal cancers. See also Table 6 (page 25), drugs approved for urologic cancers, Table 7 (page 28), drugs approved for skin cancers, and Table 8 (page 33), drugs approved for thyroid cancer. Wu further provides an illustration summarizing the protein structure of some cellular targets and the binding site of their respective drugs (Fig 12, page 38). Taken as a whole, Wu teaches that no single therapeutic has ever been identified as a treatment for all forms of cancer; and closer examination of Fig 12 provides a logical explanation: As highlighted in Fig 12, molecular protein targets implicated in different cancers (e.g. EGFR for lung cancer (see Table 1), VEGFR2 for gastric cancer (see Table 4)) have different three-dimensional protein structures, different active sites, and therefore require different drugs with the right shape and chemical groups in order to bind the target active site and have an effect in treating the cancer. In other words, there is no one size fits all approach to treating cancer simply for the reason that no single molecule will have the shape and chemical functional groups necessary to bind and modulate all molecular targets of cancer, all of which all have varied shapes. It is commonly known in the pharmaceutical arts that shape dictates function wherein drugs which have a shape complimentary to the protein target will bind and have an effect (this is often referred to simplistically as a “Lock and Key” model). Given the varied shape of protein targets in cancer (e.g. EGFR and VEGFR2), it is pure fantasy to speculate that a single drug with a single three dimensional shape will bind all protein targets implicated in cancer therapy and have an effect in treating all forms of the disease.
In view of the above, the state of the prior art and current state of the art are not aware of any “silver bullet” drug therapy to treat all forms of solid tumor cancers as is claimed presently, at least for the reason that persons skilled in the art recognize that different forms of cancer have different treatment requirements and therefore require different drug therapies. Moreover, the prior art is unaware of any agent which broadly prevents all forms of disease 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 evidence the claimed method may be useful in the of treatment of a lymphoma, a cervical tumor, a lung tumor, a colon tumor and/or metastases (see Proliferation Assays beginning at page 334; EGFR activity at page 330).
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 disorders for which there is no known association with Casein kinase 1 alpha, Casein kinase 1 delta, Bub1 kinase, or EGFR. 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 disease, 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. Applicant’s evidence does indicate any disease is prevented in human subject as is claimed.
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 § 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 8, 20, 23, 26 and 29 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:
Claim 8 recites the phrase “disorder responsive to induction of cell death”. This phrase has not been defined in the specification and renders the claim indefinite because it is unclear which conditions are regarded as a “disorder responsive to induction of cell death”.
Claims 20, 23, 26 and 29 recite the limitation "formula (Ib)" or “formula (Ia) in lines 1-2 of the claims. There is insufficient antecedent basis for these limitation in the claims because each of claims 20, 23, 26 and 29 depend from claim 1 which does not recite “formula (Ia)” or formula (Ib)”.
It is suggested claims 20 and 26 be amended to replace “formula (Ib)” with formula (I), wherein L is
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.
It is suggested claims 23 and 29 be amended to replace “formula (Ia)” with formula (I), wherein L is
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Regarding claims 23, 26 and 29 the phrases "such as” and “for example" render the claim indefinite at each occurrence because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is suggested that the phrases “such as” and “for example” be deleted from the claims.
Allowable Subject Matter
Claims 1, 3-6, 15 and 17 are allowed.
Claim 18 would be allowable if amended to overcome the objection set forth above.
Claims 20, 23, 26 and 29 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.
Reasons for allowance were provided in the previous office action.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached on (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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July 13, 2026
/K.S.M./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624
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