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 .
DETAILED ACTION
Status of the Claims
Claims 1-3 are pending. Claims 1-3 are rejected.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on application KOREA, REPUBLIC OF 10-2023-0124264, filed 09/18/2023. It is noted, however, that applicant has not filed an English translation of the certified copy of the 10-2023-0124264 application as required by 37 CFR 1.55. Therefore, the effective filing date is 09/17/2024.
Information Disclosure Statement
The information disclosure statement(s) (IDS) dated 09/17/2024 has been considered.
Claim Objections
Claim 1 is objected to because of the following informalities:
the claim could be improved by deleting the curly brackets “{“ and “}” so that the “wherein” clauses are not contained within each set of brackets. See page 1 lines 12 and 14, and page 2 lines 1, 4, 8, 10, 12 and 14.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation 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.
Claims 2 and 3 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 PKMYT1 interaction, does not reasonably provide enablement for prevention and/or treatment of cancer in general. 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/or use the invention as claimed. Accordingly, neither the intended use of claim 2 nor the method of claim 3 are enabled.
Nature of the invention:
The invention is drawn to a method of preventing or treating cancer comprising administration of a compound of Chemical Formula 1:
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, 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 Chemical Formula 1 as instantly recited to prevent or treat cancer.
State of the prior art and predictability in the art:
No compound has ever been found to prevent or 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 prevent or treat 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.
Regarding PKMYT1 inhibitors specifically, in WO 2023155871 A1, Ding et al. disclose a method for inhibiting PKMYT1 using compounds of Formula (I) for instance:
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. See Claim 1 and Example A beginning on page 81.
There do not appear to be examples in the prior art of PKMYT1 inhibitors that are able to prevent and/or treat all cancers, or even most cancers. Szychowski et al.1, for instance, demonstrated that RP-6306,
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, was an effective treatment for ovarian cancer in an in vivo study using mice implanted with OVCAR3 cells. See page 10264, last paragraph, paragraph bridging pages 10256 and 10257, as well as Figure 5A on page 10260 which shows a reduction in tumor volume in the treatment groups.
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:
Applicant demonstrates PKMYT1 inhibition using 12 compounds of Chemical Formula 1 in the assay beginning on page 50, with results shown in Table 3 on page 51. Table 2 on page 50 demonstrates Myt1 protein melting in the presence of various compounds (28) of Chemical Formula 1.
No examples have been provided that would enable the instantly disclosed compounds for preventing or treating cancer generally, as claimed in instant claim 3.
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.
Applicant may amend claim 2, for example, as follows: “A pharmaceutical composition for PKMYT1-related cancer…”.
Applicant may amend claim 3, for example, as follows: “A method for PKMYT1-related cancer…”.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-3 are rejected under 35 U.S.C. 112(b) being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999).
Where applicant is defining alternatives to hydrogen atoms on a ring, the term “substituted” in claim 1 is used by the claim to mean “replaced,” since substituted is typically used to mean that something would be further attached to the hydrogen atom. The term is indefinite because the specification does not clearly redefine the term. Applicant may overcome the rejection by amending each instance where a H atom is “substituted” with another group to “replaced”. See specifically page 1, line 14 and page 2, lines 3, 10, and 13 of the present claims.
Additionally, where claim 1 recites the definition of RY1 and RY2 as “-C1-6 alkenyl”, a person having ordinary skill in the art would recognize that a C1 alkenyl is not possible, and therefore the metes and bounds of the claim are unclear. Applicant may overcome the rejection by amending the term to “-C2-6 alkenyl”.
Dependent claims 2 and 3 are rejected as indefinite for the same reason since they do not correct the indefiniteness issue of their parent claim.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2 and 3 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
The claims recite “stereoisomers thereof” whereas claim 1 from which they depend recites “stereoisomer thereof”. Since plural stereoisomers is more broad than the singular stereoisomer of claim 1, the dependent claims are more broad than their parent claim. Applicant may overcome the rejection by amending the dependent claims to state “stereoisomer[[s]] thereof”.
Allowable Subject Matter
Claims 1-3 are free of the prior art.
The closest prior art is from Ding et al. in WO 2023155871 A1, filed February 17, 2023.
Ding et al. disclose a method for inhibiting PKMYT1 using compounds of Formula (I) for instance:
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. See Abstract and top of page 2. Example 1, see page 32:
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is nearly embraced by instant Chemical Formula 1,
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, wherein R1 is OH; R2, R3, R4 and R5 are each CH3; and X is N. The difference is that the Y1-Y4 containing ring of the instant claims must be 5-membered and aromatic and optionally fused at Y3-Y4. Ding et al. do not disclose a comparable example or genus with the fused ring at the same position flipped/rotated in such in the same manner as the instant claims. Further, Ding et al. do not provide motivation or a reasonable expectation of success in doing so in such a way as to identify the presently claimed compounds. Thus, the compounds and their compositions and methods of use thereof are both novel and nonobvious.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jalisa H. Ferguson whose telephone number is (703)756-1489. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm.
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/J.H.F./Examiner, Art Unit 1626
/REBECCA L ANDERSON/Primary Examiner, Art Unit 1626
1 Szychowski et al. “Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306” J. Med Chem. 2022, 65, 10251-10284.
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