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 .
Election/Restrictions
Applicant’s election without traverse of Group I (now claims 1-12) and species
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(hereinafter referred to as “the elected inhibitor”) in the reply filed on 2/2/2026 is acknowledged.
Claims 1-12 are pending and examined herein.
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.
112(a) Written Description
Claims 1-12 are rejected under 35 U.S.C. 112(a) 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, at the time the application was filed, had possession of the claimed invention.
Relevant to the lack of particular structural limitations in the rejected claims drawn to ---, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
Additionally, at 2163IIA3(a), the MPEP states:
“…describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene “because it is only an indication of what the gene does, rather than what it is.”); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
The claims are broadly drawn to methods of treating or preventing cancer in a subject by administering a pharmaceutical comprising a small molecule agent that is “represented by” the structures recited in the claims, included the elected inhibitor, wherein the agent inhibits Smo or Gli transcriptional activity.
In the case of the instant claims, the functionality of identifying agents that meet the functional requirements of the claim is a critical feature of the claimed methods.
The specification teaches the structure of the molecules listed in the claims. Figure 2 teaches that in vitro studies showed that these specific agents were able to inhibit Gli transcriptional activity, Gli expression, and cancer cell proliferation. However, the specification does not teach or provide any guidance as to the effect of these inhibitors in vivo, either in animal models or human clinical trials, nor does the specification provide any guidance as to the variability encompassed by the recitation of “represented by” in claim 1 or the possible modifications and variants encompassed by claim 7.
While the skilled artisan may be capable of making variants of the claimed compounds possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
The claims encompass a genus of structurally undefined inhibitors whose function is unpredictable. Even with the specific compounds recited in the claims, there is no predictability as to whether any of the agents, or variants thereof, would be capable of functioning to treat or prevent any cancer as is broadly encompassed by the claims. The specification provides no guidance as to the structure of the compounds that would function as claimed vs those that would not.
For claims drawn to a genus, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615.
Thus considering the breadth of the compounds required by the claimed methods, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
112(a) Enablement
Claims 1-12 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
There are many factors to be considered when determining whether there is sufficient evidence to support determination that a disclosure does not satisfy the enablement requirements and whether any necessary experimentation is undue. These factors have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (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 or unpredictability of the art, and (8) the breadth of the claims.”
The nature of the invention and the breadth of the claims:
The claims are broadly drawn to treating or preventing cancer in a subject by administering a pharmaceutical comprising an effective amount of at least one agent that inhibits at least one Smoothened receptor or Gli transcriptional activity, wherein the agent is the elected inhibitor.
The invention is in a class of inventions which the CAFC has characterized as 'the unpredictable arts such as chemistry and biology" (Mycolgen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Federal Circuit 2001)).
The amount of direction or guidance/Presence and absence of working examples:
The specification teaches the structure of the molecules listed in the claims. Figure 2 teaches that in vitro studies showed that these specific agents were able to inhibit Gli transcriptional activity, Gli expression, and cancer cell proliferation. However, the specification does not teach or provide any guidance as to the effect of these inhibitors in vivo, either in animal models or human clinical trials, nor does the specification provide any guidance as to the variability encompassed by the recitation of “represented by” in claim 1 or the possible modifications and variants encompassed by claim 7.
The state of the prior art and the predictability or unpredictability of the art:
While the state of the art in the field of screening and creating possible cancer therapeutics is high, the unpredictability in actually developing pharmaceutical drugs that are capable of treating or preventing cancer, let alone any cancer as broadly claimed, is much higher, including in the field of hedgehog pathway inhibitors. This is evidenced by the teachings of the prior art and the post filing date art.
McMillan (McMillan et al; Clin Cancer Res, vol 18, 4883-4888; 2012; pages 1-9) teaches that efforts to target pathogenic Hh signaling have steadily progressed from the laboratory to the clinic, where vismodegib, an SMO antagonist, has been approved for treatment of advanced BCC, Hh pathway antagonists have failed to demonstrate clinical activity in solid tumors (see abstract). McMillan teaches that a phase II study of vismodegib in ovarian cancer, the median PFS was 5.8 months for placebo and 7.5 months with vismodegib (p=0.39). Additionally, McMillan teaches that compared to placebo, the addition of vismodegib to first line chemotherapy drugs in colorectal cancer failed to significantly improve PFS vs chemotherapy alone (see page 4). Further, McMillan teaches that a trail in metastatic pancreatic cancer of saridegib and gemcitabine was halted due to the higher rate of progressive disease and lower median survival than those receiving gemcitabine alone.
Girardi (Girardi et al; Cells, vol 8, doi:10.3390; pages 1-20) teaches that the SMO inhibitor glasdegib resulted in a significant reduction in leukemic stem cell (LSC) burden in xenograft models, inhibition of Hh signaling, and a reduction in cell populations, expressing LSC markers but that a phase 1 study suggested that glasdegib had no effect on solid tumors.
Girardi teaches that eight patients achieved stable disease, and none had a complete or partial response (page 7).
Raleigh (Raleigh et al; The Journal of Clinical Investigation, vol 129, pages 465-476; 2019) teaches treatment of HH (hedgehog) pathway-associated medulloblastoma with SMO antagonists such as vismodegib can dramatically shrink tumors, but recurrence and development of acquired resistance are common and can be rapid (page 468). Raleigh teaches regarding pancreatic cancer, clinical trials of SMO antagonists for PDAC have failed to demonstrate a benefit or have been halted early for poor outcomes and that although a subset of individuals with genetically defined HH pathway-associated PDAC may benefit from targeted therapy, “the lessons learned from PDAC preclinical models and clinical testing demonstrate that HH pathway antagonists cannot be broadly applied.” (page 471). Raleigh also teaches that a significant proportion of BCC and HH associated medulloblastoma patients fail to respond to SMO inhibition and that despite clinical response in metastatic HH associated medulloblastoma, HH targeted inhibition is associated with only transient tumor regression followed by recurrence of resistant cancers (page 471). Raleigh concludes that the data suggests that molecular monotherapy may not be an effective strategy for patients with HH pathway associated cancers (page 472).
Banaszek (Banaszek et la; Journal of Cancer Research and Clinical Oncology, 2023, vol 149:17635-17649) teaches that while vismodegib and sonidegib have been approved by the FDA for targeting Hh pathway in treating BCC, none of the SMO inhibitors have been approved for therapy in sarcomas due to lack of efficacy in clinical trials (page 17642).
The level of skill in the art:
The level of skill in the art is deemed to be high.
The quantity of experimentation necessary:
To practice the invention as broadly as it is claimed. The skilled artisan would be required to test each of the claimed compounds, as well as possible variants, in animal models to determine whether any of them would be capable of treating or preventing cancer in those models. Additionally, once compounds are identified from these experimental models, extensive study and design of clinical trials in human patients would be required to establish which, if any, of the claimed compounds or their variants would be capable of functioning as claimed. This experimentation would require an enormous amount of inventive effort, with each of the many intervening steps having no guarantee of success. Additionally, as evidenced by the prior and post filing date art, the analysis would be replete with trial and error experimentation with unpredictable results.
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 1-12 are rejected under 35 U.S.C. 112(b) as 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.
Claim 1 has been amended to recite a method of treating or preventing cancer by administering a pharmaceutical “method” to a subject. However, it is not clear what the administration of a pharmaceutical method requires. Is this a typographical error or is it directed to conducting a clinical trial?
Claim 1 also recites “wherein Gli is highly expressed”, however it is not clear if the method requires that the expression of Gli be measured in subjects being treated. Additionally, the term “highly” is a term of degree which is not defined by either the specification or the claims. As such, the metes and bounds are unclear.
The recitation of “represented by” in claim 1 is indefinite because the relationship between the small molecule required by the claim and the structures in the claim are unclear. It is not clear if the term “represented by” requires the structure in the claim be administered or if it allows for variation in the chemical structure. If the latter is the case, neither the claim nor the specification provide any indication as to what variability is allowed or what the definition of the phrase “represented by” encompasses.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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