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 .
Priority
The instant application is a 35 USC 371 National Stage filing of international application No. PCT/US2021/062127, filed December 7, 2021, which claims the benefit of an effective US filing date under 35 USC 119(e) from US Provisional Applications 63/122,892; 63/146,470; 63/168,123; and 63/203,515, filed December 8, 2020; February 5, 2021; March 30, 2021 and July 26, 2021, respectively.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on March 29, 2024 and November 21, 2025 were in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the IDS documents were considered and signed copies of the 1449 forms are attached.
Election/Restrictions
Applicant’s election of breast cancer as the species of cancer to be treated, atezolizumab as the second agent, and nab-paclitaxel as the third agent in the reply filed November 21, 2025 is acknowledged.
In accordance with the MPEP, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species and the claims drawn to the elected species are allowable, the search of the Markush-type claim will be extended (see MPEP 803.02). If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. Id. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. Id. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final. Id.
As indicated above, the Examiner searched the claimed invention based on the elected species above, wherein: no prior art was discovered over the elected species. Accordingly, the scope of the search and consideration was expanded beyond the elected species to the extent necessary to find prior art. Ultimately, the full scope of formula (I) was searched and considered. Accordingly, the requirement for an election of species is no longer in effect.
Status of Claims
Currently, claims 1-5, 26-42, 71, 74 and 78-79 are pending in the instant application and under consideration herein.
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 32-34 and 39-41 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 32 recites the limitation "wherein the second agent is…" in line 1 of the claim. There is insufficient antecedent basis for this limitation in the claim since claim 30 does not include reference to a second agent.
Claim 33 recites the limitation "wherein the immune checkpoint inhibitor is…" in line 1 of the claim. There is insufficient antecedent basis for this limitation in the claim since claim 31 does not include reference to an immune checkpoint inhibitor.
Claim 34 recites the limitation "wherein the PD-L1 inhibitor is…" in line 1 of the claim. There is insufficient antecedent basis for this limitation in the claim since claim 32 does not include reference to a PD-L1 inhibitor.
Claim 39 recites the limitation "further comprising administering to the subject a therapeutically effective amount of a third agent.” There is insufficient antecedent basis for this limitation in the claim since claim 1 does not include reference to a second agent. Dependent claims 40-41 are rejected as indefinite for the same reasoning.
Appropriate correction of each instance is required
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 1-5, 26-42, 71, 74 and 78-79 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 treating PD-L1 negative breast cancer, renal cancer or urothelial cancer comprising administering a combination of eganelisib , PD-L1 inhibitor and nab-paclitaxel, does not reasonably provide enablement for a method of treating or preventing all PD-L1 negative cancer with single eganelisib therapy. 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.
The enablement rejection is focusing in all cancers as claimed.
In this regard, the application disclosure and claims have been compared per the factors indicated in the decision In re Wands, 8 USPQ2d 1400 (Fed. Cir., 1988) as to undue experimentation. The factors include:
1) the nature of the invention;
2) the breadth of the claims;
3) the predictability or unpredictability of the art;
4) the amount of direction or guidance presented;
5) the presence or absence of working examples;
6) the quantity of experimentation necessary;
7) the state of the prior art; and,
8) the relative skill of those skilled in the art.
The relevant factors are addressed below in the basis of comparison of the disclosure, the claims, and the state of the prior art in the assessment of undue experimentation.
As set forth in In re Marzocchi et al., 169 USPQ 367 (CCPA 1971):
"[A] [s]pecification disclosure which contains the teachings of manner and process of making and using the invention in terms corresponding to the scope to those used in describing and defining subject matter sought to be patented must be taken as in compliance with the enabling requirements of first paragraph of 35 U.S.C. 112, unless there is reason to doubt the objective truth of statements contained therein which must be relied on for enabling support; assuming that sufficient reasons for such doubt exists, a rejection for failure to teach how to make and/or use will be proper on that basis, such a rejection can be overcome by suitable proofs that teaching contained in the specification is truly enabling."
The Nature of the Invention
Applicant’s invention is directed to a method of treating or preventing all PD-L1 negative cancer with eganelisib. Dependent clams place limitations on the type of cancer and optionally require additional therapeutic agents for administration in the claimed method.
The State of the Prior Art/The predictability or lack thereof in the art
The state of the prior art is as follows:
As of the time of filing, a method of treating any and all cancer was unknown and the prior art did not recognize that there was a single agent or therapy capable of successfully treating all cancers which are PD-L1 negative. Ribas et al. teaches that the expression of PD-L1 in cancer cells is regulated in different ways, which leads to a different significance of its presence or absence (Abstract). In other words, it is not just the simple determination of whether a cancer is PD-L1 positive or negative which impacts the course of treatment which will be appropriate, but why the cells are PD-L1 negative that is significant. Thus, all PD-L1 negative cancers would not be expected to be treatable by the same mechanism or agent(s). Lending to the unpredictability in the art, Ribas goes on to teach that “positive PD-L1 expression in the tumors can select patients more likely to respond to these therapies…The caveat is that some patients who are tested positive for PD-L1 may not respond to the therapy, and more importantly some patients who are tested negative may still respond, making it an imperfect biomarker” (p. 2835). With respect to the clinical significance of PD-L1 negative testing, “Patients with PD-L1-negative tumors may still respond to anti-PD-1 or anti-PD-L1 therapy if given a combinatorial treatment that is able to bring T cells into tumors” (p. 2838). Accordingly, the art recognizes that a combinatorial approach is necessary to successfully treat PD-L1 negative cancer. Finally, the art describes further unpredictability specifically pertaining to cancerous tumors which have a genetic event leading to their inability to express PD-L1 (i.e. when the PD-L1 negative status is due to the genetics of the cancer cells). In this event, the tumors would not respond to interferon-gamma to increase antigen presentation, T cell attraction through chemokines, and antiproliferative effects of interferons, such that the cancer “would be unlikely to respond even to combination immunotherapies” (p. 2838).
Given that it was not known that any specific agent will be able to treat all PD-L1 negative cancers, one of ordinary skill in the art would not be able to predict that all the entirety of the claimed could be treated using the presently claimed compound, eganelisib, for mono-treatment. Given the state of the art, it is not credible that a single agent would be effective for treating such a wide scope of cancerous diseases which are notoriously difficult and unpredictable to treat, as evidenced by Ribas.
The amount of direction or guidance present/The presence or absence of working examples
MPEP §2164.03 states, "The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The 'amount of guidance or direction' refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004)...In applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required."
"Nascent technology…must be enabled with a 'specific and useful teaching'. The law requires an enabling disclosure for nascent technology because a person of ordinary skill in the art has little or no knowledge independent from the patentee's instruction. Thus, the public's end of the bargain struck by the patent system is a full enabling disclosure of the claimed technology." Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004). See MPEP §2164.03.
As established supra, the method of treating all PD-L1 cancers comprising administering the compound of claim 1 would have been unpredictable at the time of the invention, given that the art recognized the complexity of cancer, the art clearly lacked information in regards to how to treat effectively any cancer with monotherapy. Thus, the method of treatment of the invention must be considered nascent, since the state of the art at the time of the invention did not recognize the claimed objective could be accomplished with any reasonable expectation of success. As a result, the amount of guidance required from Applicant necessarily is high, since Applicant cannot rely upon what is known in the art about the nature of the invention for such guidance.
In the as-filed specification, Applicant demonstrates success in treating PD-L1 negative triple-negative breast cancer with a combination of eganelisib, atezolizumab and nab-paclitaxel.
However, Applicant fails to provide adequate working examples for how to use the mono- or dual-therapy for the treatment of any cancer, much less the full scope of PD-L1 negative cancers. Applicant as failed to demonstrate how the demonstrated activity would be extrapolated to the ability to use anything other than the three agent combination described for treating specific PD-L1 negative cancers, when there are so many factors lending to the unpredictability of medical treatment in this area. Applicant has also failed to provide any evidence, or describe any protocol, that addresses this variability in the art such that one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success in treating all claimed cancers with the claimed compound based on the direction provided in the present specification.
The quantity of experimentation to use the claimed compounds in the treatment of all cancer encompassed by the claims would be an undue burden to one of ordinary skill in the medicinal, biological and pharmacological art, since the skilled artisan is given inadequate guidance for the reasons stated above. Even with undue burden of experimentation, there is not a reasonable expectation of success that one would be able to treat all PD-L1 negativecancers in the manner claimed in view of what was known in the prior art, as evidenced by the teachings of Ribas et al. Since the reference disclosed the complexity of treating PD-L1 negative cancers, with an emphasis on the reason for the PD-L1 negativity impacting the treatment that would be expected to succeed. While the lack of working examples cannot be the sole factor in determining enablement, the absence of substantial evidence commensurate in scope with the breadth of the presently claimed subject matter, in light of the unpredictable nature of the art and the absence of direction from Applicant, provides additional weight to the present conclusion of insufficient enablement in consideration of the Wands factors as a whole.
The quantity of experimentation needed
The basis for the present rejection is not simply that experimentation would be required, since it is clear from the state of pharmaceutical, medical and chemical arts that experimentation in this art is not all uncommon, but that the level of experimentation required in order to practice these aspects of the invention in the absence of adequate enabling direction by Applicant would be undue. See In re Angstadt, 537 F.2d 498, 190 USPQ 214, 219 (CCPA 1976), which states, "The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.”
In view of the discussion of each of the preceding factors, the level of skill in the art is high and is at least that of a medicinal chemist or organic chemist with several years of experience in the art.
As the cited art and discussion of the above factors establish, the disclosure and supporting examples provided in the present specification, coupled with the state of the art at the time of the invention, fail to imbue the skilled artisan with a reasonable expectation or ability to use the full scope of the invention as instantly claimed. In order to actually use the claimed invention, it is clear from the discussion above that the skilled artisan could not rely upon Applicant’s disclosure as required by 35 U.S.C. 112(a) in order to practice the full scope of embodiments presently claimed.
Applicant is enabled for a method of treating PD-L1 negative breast cancer, renal cancer or urothelial cancer comprising administering a combination of eganelisib, PD-L1 inhibitor and nab-paclitaxel; however, the application is not enabling for the entirety of the claimed scope as described above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alicia L. Otton whose telephone number is (571)270-7683. The examiner can normally be reached on Monday - Thursday, 8:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Fereydoun Sajjadi can be reached on 571-272-0699. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALICIA L OTTON/Primary Examiner, Art Unit 1699