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
This office action is in reply to application 18/844,280 filed 05 September 2024, 371 of PCT/US2023/064237 filed 13 March 2023, with PRO 63/319,353 filed 13 March 2022. Claims 7-8, 11 and 13-14 are amended. Currently, claims 1-19 are pending.
Drawings
The drawings are objected to because several figures, i.e. Figs. 1, 4, 5, 7, etc. are not well resolved (too blurry). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
Claims 14-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
A review of the rejected claim language indicates that this claim is drawn toward “a method of treating a solid tumor in a human patient…”. A description of the term “a method of treating cancer…” may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention”. Hence, an adequate written description of the components requires more than a mere statement that it is part of the invention. The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ Application/Control Number: 18/335,687 369, 372-73 (Fed. Cir. 1984).
In Applicants’ originally filed specification, compounds of formula I are identified as inhibitors of EWS-FLI1, a potential therapeutic target for the treatment of certain cancers including Ewing sarcoma, leukemia, diffuse large B-cell lymphoma (DLBCL) and prostate cancer. However, the Applicant only demonstrates application of the claimed structures in terms of in vitro assays. Applicant does not demonstrate that the product is capable of the claimed method of treatment of the various diseases of the claim limitations to the breadth and scope of which broadest reasonable interpretation requires. Cancer is a broad class of heterogenous diseases for which there exists no general treatment or prevention. Hanahan et al. (The hallmarks of cancer, Cell 2000, 100, 1, 50-70) teaches that “there are more than 100 distinct types of cancer and subtypes of tumors can be found within specific organs (pg. 1). It is an incredibly broad field encompassing numerous possibilities that are differentiated by target, types and subtypes, patient populations, etiologies, co-morbidities, etc. teach that as a tumor progresses to a metastatic phenotype, the susceptibility to a particular treatment can differ, and as such, makes predicting the responsiveness to treatment difficult. These factors undermine the concept that in vitro cell survival results are prophetic to the final therapeutic application of the invention. Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structures, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predicable which are known to one of ordinary skill in the art, more evidence is required to show possession. One of skill in the art would not recognize from the disclosure that the applicant was in possession of a “method of treatment” for the diseases as claimed.
Additionally, it is known that there are significant challenges translating biochemical, in vitro, and in vivo studies to a clinical setting, and that not all biochemical, in vitro, and in vivo studies can be directly translated to the clinical setting. Indeed, J. M. McKim (Building a tiered approach to in vitro predictive toxicity screening: a focus on assays with in vivo resistance, Combo. Chem. & High Throughput Scr. 2010, 13, 188-206) emphasizes a truism of the pharmaceutical industry that persists to this day, is the failure of over 90% of promising new drug candidates due to unanticipated adverse effects or a lack of efficacy in humans, contrary to anticipated results based on prior biochemical, cell, or animal models (introduction). As the specification discloses working examples only performed biochemically, one of skill in the art would not recognize that the Applicant was in possession of “a method of treatment” of the various diseases and conditions claimed in an in vivo, much less a clinical, setting.
Claims 14-17 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 in vitro inhibition of ERG in Ewing’s sarcoma cell lines, leukemia cell lines, prostate cell lines, with down regulation of related gene expression, does not reasonably provide enablement for treating all cancers. 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.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a).
Upon consideration of the factors discussed below, the examiner concludes that one skilled in the art could not practice the invention without being burdened with undue experimentation based on the information provided by the applicant. A discussion of these factors as they relate to the pending claims is as follows:
(A) Breadth of claims & (B) Nature of invention –
The Applicant’s claims are broad. Claim 14 is directed to a “method of treating cancer…”. While the Applicant discloses the potential application of the product in developing new therapies for cancer, it does not demonstrate applicability, to what is known to one of ordinary skill in the art, is an incredibly broad field encompassing numerous possibilities that are differentiated by target, types and subtypes, patient populations, etiologies, co-morbidities, etc. Cancer is a broad class of heterogenous diseases for which there exists no general treatment or prevention. Hanahan teaches that “there are more than 100 distinct types of cancer and subtypes of tumors can be found within specific organs (pg. 1). The lack of specificity as to what the patient is also paints an extremely broad brush as it includes not only humans but any creature of whom this treatment may be relevant for, including mammals of which there are far too many examples to list here. As the specification discloses working examples only performed in in vitro assays, one of ordinary skill in the art would not recognize that the evidence provided by the Applicant in the instant specification is “a method of treating cancer” considering the possible breadth of what is a diverse genus that can arise from multiple factors and pathways.
(C) The state of the prior art –
The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification. See MPEP § 2164.05(a). To the best of the Examiner’s knowledge, there is no general pharmacological agent and/or pharmaceutical composition containing pharmacological agents capable of ubiquitously treating cancer. This is emphasized by Hanahan, characterizing cancer as a disease that is already “complex beyond measure” (pg. 1) and often requiring individual, tailored therapies. It is therefore reasonable to conclude that the current state of the art is highly unpredictable and extremely complex, indicating that more details, working examples, and guidance would be required to practice the invention as disclosed for treating cancer as claimed.
(D) The level of one of ordinary skill in the art –
MPEP 2141.03 states (in part), “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art' to which the claimed subject matter pertains would, of necessity, have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) disagreeing with the examiner' s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). These hurdles render application of “a method of treatment of cancer” to a very high level of unpredictability. The lack of significant guidance from the present specification makes practicing the claimed invention unpredictable. Where the predictability in the art is low, the Applicant is required to provide greater disclosure and guidance to comply with the enablement requirement. MPEP § 2164.03.
(E) Existence of working examples & (F) Amount of direction or guidance by the inventor –
As previously established by Hanahan, cancer is a complex and sophisticated disease. Conversely, the specification does not demonstrate a means to treat this broad category of disease in subjects of need to the requirement of broadest reasonable interpretation. Instead, the instant specification only provides in vitro results. Therefore, the applicant has not provided sufficient guidance to enable one of skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claim.
(G) Quantity of experimentation needed to make or use the invention –
Taken together, the prior art demonstrates that the disease arises from multiple factors and etiologies. This covers a breadth and scope of material that is far from adequately addressed in the instant specification. While the specification demonstrates in vitro inhibition, it does not demonstrate how “a compound” would be able to matriculate into a new investigational drug with a reasonable chance of success to reach the status as a demonstrative drug containing therapeutically efficacious properties. Even if the compound was not considered for human treatment, there are, established by J. M. McKim who emphasizes a truism of the pharmaceutical industry that persists to this day, is the failure of over 90% of promising new drug candidates due to unanticipated adverse effects or a lack of efficacy in humans, contrary to anticipated results based on prior biochemical cell, or animal models (introduction), introducing numerous hurdles that must be overcome for use in the broad category of a patient which is not a guaranteed, linear progression. This constitutes undue experimentation. Therefore, the lack of working examples commensurate in scope to the claimed invention and the unpredictability in successful application as described by claims 14-17, and as described in the specification, as filed, does not provide enablement for the claimed method of use.
In conclusion, the claimed invention does not provide enablement for the application in the method of use in treating the disease claimed. Thus, for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation is undue, due to the broad scope of the claim, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims, and the specification is not fully enabled for the instant claims. In view of the above, one of ordinary skill in the art would be forced into undue experimentation to practice the claimed invention.
Allowable Subject Matter
Claims 1-13 and 18-19 are allowed.
Reasons for Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: no prior art was found to encompass the general formula I nor the species listed in a 100% embodiment. Aside from the general technical field of Protacs and the bi-domain structures associated with protein degraders, no structures that read on formula I were found. Methods to synthesize these structures were correspondingly not found.
Summary
Claims 1-13 and 18-19 are allowable. Claims 14-17 are rejected under 35 U.S.C. 112(a).
Conclusion
Claims 1-13 and 18-19 are allowable. Claims 14-17 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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