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 .
Current Status of 18/569,256
This Office Action is responsive to the amended claims and Applicant remarks of 07/07/2026. Claims 67-77 and 79-86 are pending and have been examined on the merits.
Priority
The instant application is a national stage entry of PCT/EP2022/066112, filed June 14, 2022, which claims priority to European Patent Application No. 21179186.8, filed June 14, 2021, and European Patent Application No. 21179188.4, filed June 14, 2021.
Response to Arguments
Applicants have amended independent claims 67, 73, and 85 to specify that the UGT1A1 inhibitor is SCO-101 and to specify that the anticancer agent is a UGT1A1 substrate.
Rejections under 35 U.S.C. § 112(a):
The amendments to claim 85 discussed above render the previous scope of enablement rejection over the claimed method moot. The newly amended claim is no longer directed to a method comprising all UGT1A1 inhibitors and all anticancer agents. The claimed method is substantially narrower in scope and is adequately supported by the specification such that the artisan would be able to practice the claimed method without undue experimentation. The previous rejection is withdrawn.
Rejections under 35 U.S.C. §103:
Applicants argue that neither of the cited references Yashiro and Liu fail to teach a method of treating cancer comprising SCO-101, nor do the references teach treatment of patients based on RAS mutation status. These arguments have been fully considered and are persuasive. The previous rejection of the above references is withdrawn.
Claim Objections
Claims 67, 73, and 85 are objected to because of the following informalities: The structures of SCO-101 in the indicated claims are grainy and difficult to read. The substituents are difficult to interpret due to these issues. Applicants should replace these figures with clear legible figure that clearly depict the compound. Appropriate correction is required.
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 67-77 and 79-86 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while enabling for methods of treating colorectal cancer (CRC), including RAS mutated and RAS wild-type CRC, in a patient comprising administering the UGT1A1 inhibitor SCO-101 and methods for identifying a treatment regimen for a patient having CRC and treating the patient with SCO-101, does not reasonably provide enablement for the treatment or identification methods across the full scope of cancers encompassed by the claims. 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 factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to methods of treating cancer in a patient, wherein the cancer is RAS-mutated or RAS-wild-type, comprising administering SCO-101 in combination with an anticancer agent that is a UGT1A1 substrate. The claims are further drawn to methods of identifying a treatment regimen for a patient having cancer based on RAS mutation status and treating the patient with SCO-101 in combination with an anticancer agent that is a UGT1A1 substrate. Thus, the claims, when read in light of the specification, encompass methods of treatment and methods of identifying a treatment regimen applicable to all forms of cancer meeting the recited RAS-status limitations.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
The state of the prior art demonstrates that the therapeutic significance of RAS mutation status is dependent upon the particular cancer type and molecular context. Moore et al. teaches that mutation-specific biochemical properties and the tissue of origin impact the effectiveness of therapies targeting RAS-mutated cancers (Abstract). Cook et al. demonstrates that individual KRAS mutations are associated with distinct tissue-specific genetic and co-mutation profiles (Abstract). Hong et al. clinically demonstrated substantially different responses to the KRAS G-12C-directed therapy in patients having different types of cancer despite the presence of the same KRAS mutation (Abstract, Results).
Accordingly, the artisan would not reasonably have understood the relationship between RAS mutation status and treatment response demonstrated in the disclosed metastatic CRC population to be predictive of response to SCO-101 treatment regimens across all forms of cancer without further experimentation.
(5) The relative skill of those in the art:
The artisan would have experience in the field of organic chemistry, medicinal chemistry, pharmaceutical sciences, or a related field, including the design, synthesis, and development of small-molecule compounds for the treatment of cancer. The artisan would have experience evaluating the biological and pharmacological properties of candidate compounds for use in cancer therapy.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
The specification has provided guidance for clinical studies using a combination treatment regimen of SCO-101 and FOLFIRI in patients with metastatic CRC, including evaluation of treatment responses based on RAS mutation status, as well as methods of predicting treatment response with that same patient population (Examples 1-6, pgs. 53-62).
However, the specification does not provide comparable clinical guidance or working examples demonstrating the applicability of the claimed treatment or treatment-regimen identification methods to other types of cancer.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, particularly with regards to the lack of a consistent relationship between RAS mutation status and therapeutic response across different types of cancer, and the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
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 71 and 76 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.
Claims 71 and 76 recited that the anti-cancer agent is administered according to “the Summary of Product Characteristics.” The phrase “the Summary of Product Characteristics” lacks antecedent basis, and it is unclear what is encompassed by “the Summary of Product Characteristics.” Even assuming that the phrase is intended to refer to the European Union Summary of Product Characteristics for the recited anti-cancer agent, the claims rely upon an unidentified external document to establish the recommended dose required by the claims. The dosage limitation cannot be determined from the language of the claims without reference to material external to the application. The metes and bounds of the claimed dosage limitation are unclear and could not be determined with reasonable certainty by the artisan.
Claim Rejections - 35 USC § 103
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.
Claims 67-77 and 79-84 are rejected under 35 U.S.C. 103 as being unpatentable over Brunner (US 11,103,481 B2) in view of Mathijssen (Mathijssen, Ron HJ, et al. "Clinical pharmacokinetics and metabolism of irinotecan (CPT-11)." Clinical cancer research 7.8 (2001): 2182-2194.) and Yoshino (Yoshino, Takayuki, et al. "Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO–ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS." Annals of Oncology 29.1 (2018): 44-70.).
Brunner teaches a method of treating cancer comprising administering to a subject in need thereof an effective amount of a compound of general formula I
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or a pharmaceutically acceptable salt thereof, wherein the cancer is selected from a group that includes colorectal cancer (claim 1). The reference further teaches that the administered compound is a compound of formula II
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in combination with irinotecan (claim 17).. The compound of formula II is identified as SCO-101 (Col 10, lines 35-50). Col 19, lines 38-39 teach that SN-38 is the active metabolite of irinotecan. The reference does not expressly disclose SCO-101 as a UGT1A1 inhibitor, nor does it disclose methods of treating CRC based on RAS mutation status. The reference teaches oral administration of SCO-101 at a daily dosage range of 40 mg/kg/day, corresponding to 0.0809 mmol/kg/day (Example 1).
Mathijssen teaches that SN-38 is glucuronidated by UGT1A1, and therefore falls within the UGT1A1 substrate limitation of the instant claims (Abstract).
Yoshino teaches that RAS testing should be performed in all patients with metastatic colorectal cancer at the time of diagnosis because RAS mutation status was known to be predictive of response to EGFR-targeted antibody therapies, with patients having RAS-mutated tumors being unlikely to benefit from such treatment (pg. 46, right Col., final paragraph). Thus, the reference establishes that RAS mutation status was routinely determined in patients with metastatic colorectal cancer and was a recognized factor in treatment selection and expected treatment efficacy.
The artisan would have experience in oncology, pharmacology, or a related field, including the clinical use of anticancer agents, drug metabolism involving UGT1A1, and the use of molecular biomarkers such as RAS mutation status in selecting and evaluating treatment regimens for colorectal cancer.
Brunner teaches a method of treating CRC comprising administering SCO-101 in combination with irinotecan. Although Brunner does not expressly characterize SCO-101 as a UGT1A1 inhibitor, the claimed UGT1A1 inhibitory activity is an inherent property of SCO-101 and is therefore necessarily present when SCO-101 is administered. Similarly, although Brunner does not expressly characterize irinotecan or its active metabolite SN-38 as a UGT1A1 substrate, the prior art establishes that SN-38 is metabolized by UGT1A1 and is therefore a known UGT1A1 substrate. Brunner therefore teaches administration of the same therapeutic agents for the treatment of the same disease encompassed by the instant claims. The prior art further establishes that determination of RAS mutation status was routine in patients with metastatic CRC (mCRC) and was commonly used in clinical treatment selection. In view of these teachings, the artisan would have found it obvious to determine the RAS mutation status of a patient receiving the treatment regimen of Brunner and to administer the regimen to the known RAS-defined patient populations. The artisan would have reasonably expected the SCO-101/irinotecan regimen to retain its disclosed therapeutic utility for CRC when administered to such patients.
Conclusion
No claims are allowed.
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/C.K.E./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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