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 .
Applicant’s election without traverse of group I and the species PTEN deletion, prostate, MTORC1 inhibitor, Temsirolimus, and imidazole ketone erastin (IKE) in the reply filed on 7/9/26 is acknowledged.
Claims 6,11,13,15,19,21,23,34,36,38,40,42 and 44-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/9/26.
Drawings
The drawings filed on 4/15/23 are objected to for the following reasons:
37 C.F.R. 1.84 states “Character of lines, numbers, and letters. All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined.”
In the current case, the figures are not completely legible.
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.
Improper Markush Rejection
Claims 9, 17, and 22 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: Claim 9 is directed to a genus of inhibitors of different targets, each having a different sequence and activity. Inhibitors of any specific target have different structures and functions. Claim 17 is directed to a genus of MTORC1 inhibitors, each acting on different targets and each having different mechanisms. Claim 22 is directed to a genus of agents that each have different structures and act via different mechanisms. None of the agents can be substituted for another with expectation of identical activity.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. 134 and 37 CFR 41.31(a)(1).
When the Markush grouping is for alternatives of chemical compounds, they shall be regarded as being of a similar nature where the following criteria are fulfilled:
(A) All alternatives have a common property or activity; and
(B) (1) A common structure is present, i.e., a significant structural element is shared by all of the alternatives; or
(B) (2) In cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains.
In paragraph (B)(1), above, the words “significant structural element is shared by all of the alternatives” refer to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity. The structural element may be a single component or a combination of individual components linked together.
In paragraph (B)(2), above, the words “recognized class of chemical compounds” mean that there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
In order for the members of the Markush group to belong to “recognized class of chemical compounds” there must be an expectation that the members of the class will behave in the same way in the context of the claimed invention. In other words, each member of the class could be substituted one for the other with the expectation that the same intended result would be achieved. In the instant case, activity of any specific agent is dependent upon the specific structure and on the specific target that it is designed to act upon . There is no expectation that any one of the agents as claimed can be substituted for any of the others with the expectation of the same activity.
For example, small molecules have no structural relationship to shRNAs, and therefore can have no substantial structural feature in common.
As set forth in MPEP2117, “Note that where a Markush group includes only materials from a recognized scientific class of equivalent materials or from an art-recognized class, "the mere existence of such a group in an application tend[s] to prove the equivalence of its members and when one of them [is] anticipated the group [is] therefore rendered unpatentable, in the absence of some convincing evidence of some degree of non-equivalency of one or more of the remaining members." In re Ruff, 256 F.2d 590, 598-99, 118 USPQ 340, 348 (CCPA 1958)("[A]ctual equivalence is not enough to justify refusal of a patent on one member of a group when another member is in the prior art. The equivalence must be disclosed in the prior art or be obvious within the terms of Section 103." Id. at 599, 118 USPQ at 348).”
In the instant case, art against any one agent would not be evidence against any of the remaining members that have different structures and do not have identical activity.
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 1, 2, 8, 9, 17, and 22 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.
Instant claim 1 requires administering (a) an inhibitor of the PI3K/Akt/MTOR signaling axis and (b) an inducer of ferroptosis, thereby reducing the growth of and/or causing regression of the tumor in the subject.
The specification does not adequately describe the structure required for the function for an agent to be an inhibitor of the PI3K/Akt/MTOR signaling axis or an inducer of ferroptosis. The species of the specification are not representative of the entire claimed genus. Without further description of the specific structure required to function as an inhibitor of the PI3K/Akt/MTOR signaling axis or an inducer of ferroptosis, one would not be able to readily recognize which agents have the structure to function as an inhibitor of the PI3K/Akt/MTOR signaling axis or an inducer of ferroptosis.
With regards to claim 9, the specification does not adequately describe the structure require for the agent to function as a PI3K inhibitor, an Akt inhibitor, an MTOR inhibitor, an MTORC1 inhibitor, an SREBP inhibitor, or a SCD1 inhibitor.
With regards to claim 17, the specification does not adequately describe the structure require for the agent to function as a short hairpin RNA (shRNA) inhibitor of RAPTOR. It is known that not any shRNA directed to a specific target results in inhibition. Additionally, the claim does not require for the shRNA to have any structural relationship with any specific target sequence, but rather encompasses shRNAs targeted to other targets that have the secondary effect of inhibiting RAPTOR, a genus of agents that have not been adequately described in the specification.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species that have the structure required to function as claimed. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 8, 9, 17, and 22 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Pandolfi et al. (WO 2019/140257 A1).
Pandolfi et al. teach: a method for treating prostate cancer in a subject, the method comprising administering an agent that inhibits AKT/mTOR or MAPK signaling (page 1).
Pandolfi et al. teach: The method for treating prostate cancer in a selected subject involves administering to the subject an agent that inhibits AKT/mTOR or MAPK signaling, where the subject is selected by detecting co-deletion of Phosphatase And Tensin Homolog (PTEN) and Promyelocytic Leukemia (PML) or amplification of Protein Phosphatase 1 Catalytic Subunit Alpha (PPP1CA). The subject is selected by characterizing a biological sample of the subject for co-deletion of PTEN and PM, amplification of PPP1CA, and/or activation of Sterol regulatory element-binding transcription factor 1 (SREBP) (page 2) (instant claims 2 and 8).
Pandolfi et al. teach: The agent is one that inhibits AKT/mTOR is Temsirolimus (page 24) (instant claims 9 and 17).
Pandolfi et al. do not teach the addition of an inducer of ferroptosis, but do teach utilizing various combination therapies including altretamine (pages 24-25) (instant claim 22), which meets the limitation of being a ferroptosis inducer as required in claim 1 by being recited as one in claim 22.
Therefore, the claims are anticipated by Pandolfi et al.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 2, 8, 9, 17, and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pandolfi et al. (WO 2019/140257 A1), as set forth above, further in view of Zhao et al. (OncoTargets and Therapy 2020:13 5429–5441,published 6/11/20), and Zhang et al. (Ferroptosis in Health and Disease, published 10/11/19, Chapter 18, pages 303-324).
The instant rejection is directed to the elected species of ferroptosis inducer, imidazole ketone erastin (IKE).
Pandolfi et al. teach: a method for treating prostate cancer in a subject, the method comprising administering an agent that inhibits AKT/mTOR or MAPK signaling (page 1).
Pandolfi et al. teach: The method for treating prostate cancer in a selected subject involves administering to the subject an agent that inhibits AKT/mTOR or MAPK signaling, where the subject is selected by detecting co-deletion of Phosphatase And Tensin Homolog (PTEN) and Promyelocytic Leukemia (PML) or amplification of Protein Phosphatase 1 Catalytic Subunit Alpha (PPP1CA). The subject is selected by characterizing a biological sample of the subject for co-deletion of PTEN and PM, amplification of PPP1CA, and/or activation of Sterol regulatory element-binding transcription factor 1 (SREBP) (page 2) (instant claims 2 and 8).
Pandolfi et al. teach: The agent is one that inhibits AKT/mTOR is Temsirolimus (page 24) (instant claims 9 and 17).
Pandolfi et al. do not teach the addition of an inducer of ferroptosis, but do teach utilizing various combination therapies including altretamine (pages 24-25) (instant claim 22), which meets the limitation of being a ferroptosis inducer as required in claim 1 by being recited as one in claim 22.
With regards to the elected species, imidazole ketone erastin (IKE),
Zhao et al. teaches that erastin can induce ferroptosis, causing cell death in cancer cells. Zhao et al. teach that erastin is able to enhance the sensitivity of chemotherapy and radiotherapy, suggesting a promising future in cancer therapy (abstract) (instant claim 22).
Zhao et al. teaches that ferroptosis can inhibit the proliferation of malignant cells in prostate cancer (page 5429). Zhao et al. teaches that LNCaP cells sensitivity to cell death induced by erastin was significantly increased upon overexpression of ACSL4 in these human prostate cancer cells (page 5435). Zhao et al. teaches that erastin differs from other ferroptosis inducers in that the latter usually trigger a single pathway, whereas erastin can trigger multiple molecules and the effect is efficient, rapid, and lasting (pages 5429-5430).
It would have been obvious to include erastin in the composition of Pandolfi et al. with a reasonable expectation of treatment of prostate cancer in the method of Pandolfi et al. because both Temsirolimus and erastin were known to treat prostate cancer. It is obvious to combine compounds that are useful individually for the same purpose.
It would have been obvious to utilize imidazole ketone erastin instead of erastin as a matter of design choice because each were known to induce ferroptosis and the benefits of imidazole ketone erastin compared to erastin were known. Zhang et al. teach that piperazine ketone erastin (PKE) and imidazole ketone erastin (IKE) are two types of ketone erastin analogues. These drugs block the metabolic degradation of cytochrome P450 enzyme at its sensitive location. These compounds demonstrate increased water solubility and stability in the body and therefore are more effective for ferroptosis induction compared to erastin, and IKE is two times as effective compared to PKE (page 314). Zhang et al. teaches that LNCaP prostate cancer cells exhibit hypersensitivity to ferroptosis (page 309). Therefore, there would have been a motivation and a reasonable expectation of success of more effective ferroptosis induction with IKE (instant claim 22).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636
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