Detailed Action
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 the Claims
Claims 1-4, 6-17 and 19-22 are pending. Claims 1-4, 6-8, 10-17 and 19-22 are rejected. Claim 9 is objected to.
Information Disclosure Statement
The Information Disclosure Statements (IDS’s) submitted on 2/19/2024, 8/21/2024, and 9/9/2025 were considered by the Examiner.
Priority
This is a 35 U.S.C. 371 National Stage Filing of International Application No.
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, which claims priority under 35 U.S.C. 119(a-d) to
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. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d).
Election/Restriction
In view of English translation of Priority Document 202110188129X received on 12/25/2025, the requirement for restriction, mailed 11/6/2025 has been withdrawn; the priority date of the instant claims is 2/10/2021. Consequently, Applicant’s remarks from 12/25/2025 will not be addressed. Claims 1-4, 6-17 and 19-22 have been examined in full.
Claim Objections
Claim 6 is objected to because of the following informalities: On line 3 of p. 10, Examiner recommends replacing “any of the following compounds” with “selected from the group consisting of” and replacing the “or” on p. 11 with “and”. Appropriate correction is required.
Claim 7 is objected to because of the following informalities: On line 3 of p. 11, Examiner recommends replacing “any of the following compounds” with “selected from the group consisting of” and inserting an “and” directly preceding the last compound listed on p. 14. Appropriate correction is required.
Claim 9 is objected to because of the following informalities: Claim should begin with “A”. Appropriate correction is required.
Claim 20 is objected to because of the following informalities: On lines 3-4, replace “tablet, capsule, pellet, powder, granule, elixir, tincture, suspension, syrup, emulsion or solution” with “a tablet, a capsule, a pellet, a powder, a granule, an elixir, a tincture, a suspension, a syrup, an emulsion or a solution”. Appropriate correction is required.
Claim Interpretation
Claims 11 and 19 are being interpreted as to be only administration of the compound according to claim 1. While the claims recite that it could be used in combination, the claim does not specifically recite the actual administration of the second “other drug”.
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 1-4, 6-8, 10-17 and 19-22 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 1, p. 2, line 2, refers to “their”, which is unclear and a personal pronoun. “The meaning of every term used in a claim should be apparent from the prior art or from the specification and drawings at the time the application is filed. Claim language may not be "ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention." In re Packard, 751 F.3d 1307, 1311, 110 USPQ2d 1785, 1787 (Fed. Cir. 2014). Since “their” is a personal pronoun, it is unclear to which it previous refers. Examiner recommends replacing “their” with a non-personal pronoun to enhance clarity of the record, such as “a”. Claim 2, p. 6, line 2; Claim 3, p. 7, line 2; Claim 4, p. 8, line 2; Claim 6, p. 10, line 2; Claim 7, p. 11, line 2; Claim 10, line 3; Claim 11, line 9; Claim 12, p. 16, line 1; Claim 13, line 3; Claim 14, p. 16, line 2; Claim 15, p. 17, line 2; Claim 16, p. 18, line 2; Claim 17, p. 19, line 2; Claim 21, p. 20, line 2; Claim 22, line 2, have the same issue. Claims 8, 19, and 20 are additionally rejected for depending from an indefinite claim and failing to remedy its deficiencies.
Claim 1, p. 2, line 2, refers to “isotope-labeled derivative”. The metes and bounds of this limitation, specifically the term “derivative” cannot be ascertained from the instant disclosure. The instant disclosure refers to “isotope-labeled compound [of formula (I)]” (see ie. Para. [0006] of the instant specification), which removes ambiguity when specifically referring to the structure of formula (I). Examiner recommends replacing the word “derivative” in claim 1 to “compound of”. Claim 8 is rejected for depending from an indefinite claim and failing to remedy its deficiencies.
Claim 1, R1 definition on p. 2 and claim 21, R1 definition on p. 20 recite the following on the second lines:
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, which include stereobonds that are too blurry to differentiate between bolded, dashed, or squiggly. Examiner requires clarifying this issue with new images of structures. Also, for the purpose of compact prosecution, Examiner is accepting all stereochemistry scenarios of the above substituents.
Claim 2 recites the limitation "isotope-labeled compound" in lines 2-3, p. 6. There is insufficient antecedent basis for this limitation in the claim. The analogous definition in independent claim 1 is “isotope-labeled derivative”. Because of support and clarity in the instant specification for “isotope-labeled compound”, Examiner recommends maintaining consistency throughout the claims, especially instant claim 1, with the “compound” language. Claim 3, p. 7, lines 2-3; Claim 4, p. 8, lines 2-3; Claim 6, p. 10, line 2; Claim 7, p. 11, line 2; Claim 10, lines 3-4; Claim 11, line 9; Claim 12, p. 16, line 1; Claim 13, line 3; Claim 14, p. 16, lines 2-3; Claim 15, p. 17, lines 2-3; Claim 16, p. 18, lines 2-3; Claim 17, p. 19, lines 2-3; Claim 21, p. 20, line 2; Claim 22, line 2, have the same issue. Claims 19 and 20 are additionally rejected for depending from an indefinite claim and failing to remedy its deficiencies.
Claim 2, p. 7, refers to two various instances of when R2 may be “an amino group substituted by C1-4 alkyl”, separated by the word “or” (see lines 17-20). The term “or” indicates that the various scenarios are exclusive, however these two overlap (methyl, ethyl or C1-4 is 1 or 2). It is unclear to Examiner that Applicant intended for these two scenarios to truly be exclusive. Examiner recommends deleting one or the other to clarify the record.
Claim 7 contains the trademark/trade name “DAICEL CHIRALPAK IG”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the chromatography column used and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 112
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.
The rejection of Claims 10 and 11 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 Embryonic ectoderm Development (EED) in Polycomb Repressive Complex 2 (PRC2), treatment of a rhabdoid tumor, and treating B-cell non-Hodgkin’s lymphoma, does not reasonably provide enablement for treatment of cancer in general, or treatment of the cancers recited apart from the aforementioned indications is maintained. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Nature of the invention:
The invention is drawn to a method of treating cancer comprising administration of a compound of formula (I) as recited in instant Claim 1.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to administration of any of the numerous compounds encompassed by a formula (I) as instantly recited to treat cancer.
State of the prior art and predictability in the 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 of any pharmaceutical agents that are useful in the treatment of cancer generally. At Page 1004, 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”. 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. 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 environmental 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 Cartright, 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 Applicant’s 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.
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, 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. As such, at present the “silver bullet” drug therapy to treat all forms of cancer is elusive and such a therapy is not recognized in the art where the reality is that different forms of cancer require different drug therapies.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
Beginning at page 113, sufficient disclosure is provided enabling the instantly disclosed compounds as EED target inhibitors.
Beginning at page 116, sufficient disclosure is provided enabling the instantly disclosed compounds as suitable for treatment of G401 cells. The G401 cell line is derived from a rhabdoid tumor of the kidney. Therefore, the instantly disclosed compounds are enabled for the treatment of a rhabdoid tumor.
Beginning at page 121, sufficient disclosure is provided enabling the instantly disclosed compounds for the inhibition of KARPAS-442 cells, which are human B-cell non-Hodgkin’s lymphoma cells. Therefore, the instantly disclosed compounds are enabled for the treatment of B-cell non-Hodgkin’s lymphoma.
No examples have been provided that would enable the instantly disclosed compounds for treating various other cancers as recited in claims 11, including liver cancer, prostate cancer, colon cancer, etc.
Quantity of experimentation needed to use the invention
The quantity of experimentation needed is undue experimentation. A person having ordinary skill in the art would need not only to identify and/or develop metrics to be able to investigate the efficacy of the disclosed compounds in the treatment of cancer generally, but would also need to evaluate the disclosed compounds, with no assurance of success.
The Applicant has not sufficiently disclosed examples demonstrating the efficacy of the instantly claimed compounds in treating cancer generally. The utility thereof would not have been readily recognized by a person having ordinary skill in the art at the time of filing, as distinct cancers have mutually exclusive etiologies. The examples disclosed in the application are not sufficient to overcome the unpredictability of treating cancer generally.
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.
Genentech Inc. V Novo Nordisk A/S (CAFC) 42 USPQ 2d 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 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 having ordinary skill in the art would have to engage in undue experimentation to determine the efficacy of disclosed compounds in treating cancer, with no assurance of success.
Closest Prior Art
The closest prior art to instant claims 1-4, 6-8, 10-17 and 19-22 is US20160176882. US20160176882 teaches the following compound, useful for a PRC2-mediated disease or disorder (arrow added by Examiner):
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(see abstract and bottom right of p. 5). The prior art compound differs in connectivity and structure from the instant claims in multiple locations, including that of the added arrow. The prior art compound shows a heterocyclic ring with oxygen at the location of the arrow, whereas the instant claims have a heterocyclic ring with multiple nitrogens. Therefore, the prior art does not provide motivation for, nor render obvious, the instant claims.
The closest prior art to instant claim 9 is CAS Registry No. 1889793-92-3 (which entered the STN database on 4/14/2016). CAS Registry No. 1889793-92-3 is drawn to the following structure:
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, which differs from a compound of instant claim 9 in two regards. 1) the Br is a positional isomer and 2) the R3’s of the prior art are methyl, wherein the instant claims may be fluoro substituted methyl. Therefore, the prior art does not provide motivation for, nor render instant claim 9 obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MEGHAN C HEASLEY whose telephone number is (571)270-0785. The examiner can normally be reached Monday - Friday 8:30-4:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MEGHAN C HEASLEY/Examiner, Art Unit 1626