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 Claims
Claims 26,31 and 34-51 are pending in the instant application. Claims 46-51 are new and drawn to the elected invention. Of these claims, claims 46, 47, and 51 read on
the elected species. Claims 38,41,43-45, and 48-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. An action on the merits of claims 26,31,34-37,39-40,42,46-47, and 51 is contained herein.
Information Disclosure Statement
The examiner has considered the information disclosure statement filed most recently of record.
Previous Objections/Rejections
Any rejections or objections stated of record in the office action mailed on 4/11/2025 that are not explicitly addressed herein below, are hereby withdrawn in light of applicant's arguments and/or amendments filed 9/10/2025.
35 USC § 112 (a)
The rejection of claims 26,31,34-37,39-40, and 42 is maintained.
Applicant’s amendments and arguments, see Remarks, filed 9/10/2025, with respect to the rejection set forth in the Non-Final Office Action mailed 4/11/2025, have been fully considered but are not found persuasive.
To summarize the rejection of record, 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. The state of the prior art is most relevant to the enablement rejection in the instant case. For example, a number of papers have been published in the literature describing the PI3-AKT signaling pathway and their relationship to the regulation of cell cycle proliferation. In particular, inhibitors of this pathway in treating disease states such as hyperproliferative disorders is still under investigation (Cancers (Basel), Sirico et al. Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy, 2023 Feb; 15(3): 703). There has yet to be seen any approval of these drugs in clinical practice due to issues such as poor selectivity and adverse side effects (see page 23, Summary and Conclusions section). Additionally, the compounds under clinical investigation appear to be used in an inhibitory manner to suppress activity (note the claims encompass language wherein the term modulation in the broadest sense may encompass both inhibitory or agonistic modes of action). Therefore, the ability of the claimed compounds to be used in the manner claimed is highly unpredictable.
Applicants argue that the most recent submitted references of record (see Zhang et al. along with Freudlsperger et al.) along with limiting the claims to recite squamous cell cancer as the disease obviates the enablement rejection. The examiner respectfully disagrees. Applicants are reminded that the clams are not only to the treatment of this particular set of cancers but also to the prevention. As stated previously, the only limited information provided is in vitro inhibitory data shown at page 186. No in vivo or additional information is provided as to how to extrapolate this limited information for enabling the treatment/prevention of squamous cell cancer. Even more concerning is the calculated inhibitory data regarding the claimed compounds which possess unpromising IC50 ranging from 35nM to an unremarkable 956 nM (see page 190 of disclosure) which does not appear to be promising in terms of treatment.
In regard to the submitted references; the information provided therein is simply speculative in regard to treating particular types of squamous cell carcinomas which include esophageal, head, and neck (see abstract with language such as “possible routes”, etc.). The references are also silent with regard to any potential preventative measures of squamous cell carcinomas via PI3K inhibition as required in the claims as well.
Lastly, the assertions are circumvented by the more recent references cited by the examiner. In particular, inhibitors of this pathway in treating disease states such as hyperproliferative disorders is still under investigation (Cancers (Basel), Sirico et al. Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy, 2023 Feb; 15(3): 703). There has yet to be seen any approval of these drugs in clinical practice due to issues such as poor selectivity and adverse side effects (see page 23, Summary and Conclusions section). Applicants have not addressed this most recent reference regarding the state of the art and also the unpromising IC50 data of the claimed compounds ranging from 35nM to an unremarkable 956 nM. Therefore due to the lack of definitive information in the most recent submitted references and deficient data presented in the specification the rejection is maintained.
New Rejections
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 46, 47, and 51 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 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.
Pursuant to In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required:
(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.
Some experimentation is not fatal; the issue is whether the amount of experimentation is "undue"; see In re Vaeck, 20 USPQ2d 1438, 1444. Analysis of sections (A)-(F) is described below:
(A) Breadth of claims: The claims are drawn to the treatment (as well as the prevention) of a disease or disorder in a mammal by modulation of the P13K-Akt or mTOR signal transduction pathway via modulation of one or more related enzymes using the instantly claimed compounds; wherein modulation may encompass both inhibitory or agonistic modes of action. The diseases are limited to squamous cell cancer; however the scope of the latter may incorporate cancers associated with a myriad of organs including skin, mouth, lungs, etc. Based on the above analysis, the claims are very broad.
(B) The nature of the invention: The nature of the invention is related to the modulation of biological pathways for treating disease states such as cancer. More specifically, the instant invention is drawn to the treatment or prevention of physiological states and/or pathological states in a mammal by modulation of the P13K-Akt signal transduction pathway. Modulation of said signal pathway is achieved by the modulation of one or more related enzymes using compounds of formula I; wherein modulation may encompass inhibitory or agonistic modes of treatment. Overall, the nature of the invention may be construed to one of ordinary skill as very complex.
(C) State of the Prior Art:
A number of papers have been published in the literature describing the PI3-AKT signaling pathway and their relationship to the regulation of cell cycle proliferation. In particular, inhibitors of this pathway in treating disease states such as hyperproliferative disorders is still under investigation (Cancers (Basel), Sirico et al. Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy, 2023 Feb; 15(3): 703). There has yet to be seen any approval of these drugs in clinical practice due to issues such as poor selectivity and adverse side effects (see page 23, Summary and Conclusions section). Additionally, the compounds under clinical investigation appear to be used in an inhibitory manner to suppress activity (note the claims encompass language wherein the term modulation in the broadest sense may encompass both inhibitory or agonistic modes of action).
Therefore, the ability of the claimed compounds to be used in the manner claimed is highly unpredictable.
(D) Skill of those in the art: The level of skill in the art is high and one would possess a Ph.D. in synthetic organic chemistry or chemical biology.
(F) Direction or Guidance: Little guidance or direction is provided by Applicant in reference for treating diseases falling within the claim scope including the elected species of epithelial squamous cell cancer. The only limited information provided is in vitro inhibitory data shown at page 186. No in vivo or additional information is provided as to how to extrapolate this limited information for enabling the treatment/prevention of the elected species or other diseases. Even more concerning is the calculated inhibitory data regarding the claimed compounds which possess unpromising IC50 ranging from 35nM to an unremarkable 956 nM (see page 190 of disclosure) which does not appear to be promising in terms of treatment.
Based on the preponderance of evidence described in section (C) detailing the current state of P13K inhibition for treating disease, one of ordinary skill would expect undue experimentation executing the claimed method using the compounds of formula I.
Due to the level of unpredictability in the art, the very limited guidance provided, and the lack of working examples, the applicant has shown lack of enablement. MPEP 2164.01(a) states, "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. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." That conclusion is clearly justified here.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN E MCDOWELL whose telephone number is (571)270-5755. The examiner can normally be reached on 8:30-6 MF.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN MCDOWELL/
Primary Examiner, Art Unit 1624